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Journal articles on the topic 'CD8-Positive T-Lymphocytes Immunotherapy'

Author: Grafiati

Published: 4 June 2021

Last updated: 19 February 2022

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1

Ruan, S., D. R. Samuelson, B. Assouline, M. Morre, and J. E. Shellito. "Treatment with Interleukin-7 Restores Host Defense against Pneumocystis in CD4+T-Lymphocyte-Depleted Mice." Infection and Immunity 84, no. 1 (2015): 108–19. http://dx.doi.org/10.1128/iai.01189-15.

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Pneumocystispneumonia (PCP) is a major cause of morbidity and mortality in patients with HIV infection. CD4+T lymphocytes are critical for host defense against this infection, but in the absence of CD4+T lymphocytes, CD8+T lymphocytes may provide limited host defense. The cytokine interleukin-7 (IL-7) functions to enhance lymphocyte proliferation, survival, and recruitment of immune cells to sites of infection. However, there is little known about the role of IL-7 in PCP or its potential use as an immunotherapeutic agent. We hypothesized that treatment with recombinant human IL-7 (rhIL-7) woul

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Whiteside, TL, EM Elder, D. Moody, et al. "Generation and characterization of ex vivo propagated autologous CD8+ cells used for adoptive immunotherapy of patients infected with human immunodeficiency virus." Blood 81, no. 8 (1993): 2085–92. http://dx.doi.org/10.1182/blood.v81.8.2085.2085.

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Abstract Cytolytic T lymphocytes play an important role in host defense against viral infections, including human immunodeficiency virus (HIV). In a phase I clinical trial (protocol 080 of the AIDS Clinical Trials Group), generation of CD8+ effector cells from peripheral blood of patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS and safety of autologous adoptive transfer of these cells were evaluated. For therapeutic infusions, CD8+ T cells were purified by positive selection on anti-CD8 monoclonal antibody-coated flasks from leukapheresed peripheral blood o

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Whiteside, TL, EM Elder, D. Moody, et al. "Generation and characterization of ex vivo propagated autologous CD8+ cells used for adoptive immunotherapy of patients infected with human immunodeficiency virus." Blood 81, no. 8 (1993): 2085–92. http://dx.doi.org/10.1182/blood.v81.8.2085.bloodjournal8182085.

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Cytolytic T lymphocytes play an important role in host defense against viral infections, including human immunodeficiency virus (HIV). In a phase I clinical trial (protocol 080 of the AIDS Clinical Trials Group), generation of CD8+ effector cells from peripheral blood of patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS and safety of autologous adoptive transfer of these cells were evaluated. For therapeutic infusions, CD8+ T cells were purified by positive selection on anti-CD8 monoclonal antibody-coated flasks from leukapheresed peripheral blood of seven p

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4

Nishimura, Toshinobu, Shin Kaneko, Yoko Tajima, et al. "In Vitro Generation of Mature T Lymphocytes From Human Ips Cells and Genetic Analysis of TCR Gene Rearrangements." Blood 118, no. 21 (2011): 2984. http://dx.doi.org/10.1182/blood.v118.21.2984.2984.

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Abstract Abstract 2984 T lymphocytes play central roles in cellular immunity, exerting their proliferative and effector activities when they recognize antigens via T-cell receptors (TCRs) in HLA-restricted and antigen-specific manner. Adoptive cell transfer therapy (ACT), the administration of ex vivo-activated and -expanded autologous tumor-reactive T lymphocytes, is currently one of the effective methods for immunotherapy, especially for treatment of metastatic solid tumors including melanoma. However, the successful applications of this method are currently limited for tumor therapies. To b

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Yee, Cassian, John A. Thompson, Patrick Roche, et al. "Melanocyte Destruction after Antigen-Specific Immunotherapy of Melanoma." Journal of Experimental Medicine 192, no. 11 (2000): 1637–44. http://dx.doi.org/10.1084/jem.192.11.1637.

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Current strategies for the immunotherapy of melanoma include augmentation of the immune response to tumor antigens represented by melanosomal proteins such as tyrosinase, gp100, and MART-1. The possibility that intentional targeting of tumor antigens representing normal proteins can result in autoimmune toxicity has been postulated but never demonstrated previously in humans. In this study, we describe a patient with metastatic melanoma who developed inflammatory lesions circumscribing pigmented areas of skin after an infusion of MART-1–specific CD8+ T cell clones. Analysis of the infiltrating

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Sharma, P., E. Sato, D. Bajorin, et al. "CD8+ tumor-infiltrating lymphocytes as a statistically significant marker of disease recurrence and survival in transitional cell carcinoma patients." Journal of Clinical Oncology 24, no. 18_suppl (2006): 4544. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.4544.

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4544 Background: Superficial transitional cell carcinoma (TCC) is an immune-responsive tumor evidenced by immunotherapy trials with BCG demonstrating improved survival. In contrast, more advanced muscle-invasive TCC is not considered an immunologically active tumor. Yet, host immune functions that may have a clinical impact on the biologic activity of these more invasive tumors have not been systemically evaluated. CD8+ T-cells are responsible for cytotoxicity and potential tumor eradication by interaction with antigen plus human leukocyte antigens (HLA). A clear association between intratumor

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Yasukawa, Masaki, Hironari Niiya, Taichi Azuma, et al. "Generation of Tumor-Specific CD8+ Cytotoxic T Lymphocytes and CD4+ Th1 Helper T Cells by Transfer of T-Cell Receptor Genes Isolated from a WT1-Specific CD8+ Cytotoxic T-Lymphocyte Clone." Blood 104, no. 11 (2004): 2523. http://dx.doi.org/10.1182/blood.v104.11.2523.2523.

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Abstract Background: Cytotoxic T lymphocytes (CTLs) and T-helper type 1 (Th1) cells undoubtedly play a crucial role in the eradication of tumors in vivo. However, the production of Th1 cytokines such as IL-2 and IFN-γ is markedly suppressed in the majority of tumor-bearing hosts. Such defects in Th1-mediated immunity in cancer patients have made it difficult to induce tumor-specific CTLs that promote tumor rejection. Adoptive transfer of tumor-specific CTLs and Th1 cells can overcome the difficulty to induce tumor-specific immune response in cancer patients; however, the generation and expansi

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Ohminami, Hideki, Masaki Yasukawa, and Shigeru Fujita. "HLA class I-restricted lysis of leukemia cells by a CD8+ cytotoxic T-lymphocyte clone specific for WT1 peptide." Blood 95, no. 1 (2000): 286–93. http://dx.doi.org/10.1182/blood.v95.1.286.

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Abstract The Wilms tumor (WT1) gene has been reported to be preferentially expressed in acute leukemia cells, regardless of leukemia subtype and chronic myelogenous leukemia cells in blast crisis, but not in normal cells. This finding suggests strongly that WT1 protein is a potential target of immunotherapy for human leukemia. In this study, we established a CD8+ cytotoxic T-lymphocyte (CTL) clone directed against a WT1-derived peptide and examined its immunologic actions on leukemia cells. A CD8+ CTL clone, designated TAK-1, which lysed autologous cells loaded with a WT1-derived 9-mer peptide

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Ohminami, Hideki, Masaki Yasukawa, and Shigeru Fujita. "HLA class I-restricted lysis of leukemia cells by a CD8+ cytotoxic T-lymphocyte clone specific for WT1 peptide." Blood 95, no. 1 (2000): 286–93. http://dx.doi.org/10.1182/blood.v95.1.286.001k48_286_293.

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The Wilms tumor (WT1) gene has been reported to be preferentially expressed in acute leukemia cells, regardless of leukemia subtype and chronic myelogenous leukemia cells in blast crisis, but not in normal cells. This finding suggests strongly that WT1 protein is a potential target of immunotherapy for human leukemia. In this study, we established a CD8+ cytotoxic T-lymphocyte (CTL) clone directed against a WT1-derived peptide and examined its immunologic actions on leukemia cells. A CD8+ CTL clone, designated TAK-1, which lysed autologous cells loaded with a WT1-derived 9-mer peptide consisti

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Mitchell, Malcolm S., Denise Darrah, David Yeung, et al. "Phase I Trial of Adoptive Immunotherapy With Cytolytic T Lymphocytes Immunized Against a Tyrosinase Epitope." Journal of Clinical Oncology 20, no. 4 (2002): 1075–86. http://dx.doi.org/10.1200/jco.2002.20.4.1075.

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PURPOSE: To study distribution and toxicity of cytolytic T lymphocytes (CTLs) against a single melanoma epitope. PATIENTS AND METHODS: CD8+ T cells obtained by leukapheresis from 10 patients with disseminated HLA-A2.1+, tyrosinase-positive melanomas were immunized in vitro against tyrosinase369-377 (YMNGTMSQV). Drosophila cells transduced with HLA-A2.1, CD80, and CD54 (intracellular adhesion molecule-1) were used for priming, followed by two rounds of immunization with mononuclear cells as antigen-presenting cells. 1 × 108 CTL were infused intravenously (IV) on day 1. CTL frequency was measure

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Shin, David, Nikhil Lamba, Catherine Flores, et al. "TMIC-08. IDENTIFICATION OF TUMOR SPECIFIC LYMPHOCYTES IN A MURINE GLIOMA MODEL." Neuro-Oncology 21, Supplement_6 (2019): vi248. http://dx.doi.org/10.1093/neuonc/noz175.1042.

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Abstract INTRODUCTION One major challenge in the use of immunotherapy for glioblastoma is the identification of tumor specific lymphocytes within the tumor microenvironment. Previous studies in non-glioma cancer models have identified CD39 and PD1 as lymphocyte markers of tumor specificity. In this study, we demonstrate the existence of this specific T cell phenotype and show correlation with anti-tumor activity. METHODS We implanted KR158B murine glioma cells into right caudate nucleus into yellow fluorescent protein (YFP) interferon-gamma reporter mice for a total of 104 cells using stereota

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Cortivo, Liliane Dal, Mathilde Bahuaud, Marie Noelle Lacassagne, Vincent Monchois, Cecile Ducasse, and Marina Cavazzana-Calvo. "Anti CMV Immunotherapy with Donor Antigen Specific Lymphocytes Selected with GMP HLA Class 1 Tetramer Reagents." Blood 114, no. 22 (2009): 4492. http://dx.doi.org/10.1182/blood.v114.22.4492.4492.

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Abstract Abstract 4492 Patients undergoing allogeneic haematopoietic stem cell transplants frequently develop infections that are responsible for a high rate of morbidity and mortality during first 6 months post transplantation. The occurrence of CMV infection might reach 70% to 80% of transplanted patients; this rate is increased in HSC transplantations conditioned by in vivo and/or in vitro immunosuppressive treatment. Prophylactic treatment of CMV infection by ganciclovir or foscarnet, though proven to be efficient, faces complications such as myelotoxicity, nephrotoxicity and/or the develo

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Filaci, Gilberto, Marco Fravega, Maurizio Setti, et al. "Frequency of telomerase-specific CD8+ T lymphocytes in patients with cancer." Blood 107, no. 4 (2006): 1505–12. http://dx.doi.org/10.1182/blood-2005-01-0258.

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Telomerase is considered a universal tumor-associated antigen (TAA) due to its high rate of expression by cancers (≈90%), and clinical trials are in progress to test the immunotherapeutical efficacy of antitelomerase immunization in patients with cancer. However, the data concerning frequency and functional activity of telomerase-specific cytotoxic T lymphocytes (CTLs) in patients with cancer are few and conflicting, although their knowledge would be mandatory to predict the efficacy of telomerase-specific immunotherapy in selected patients. We performed this study to analyze frequency and cyt

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Okamura, Kazumi, Satoshi Nagayama, Tomohiro Tate, Kazuma Kiyotani, and Yusuke Nakamura. "The potential target of double negative T cells in cancer immunotherapy." Journal of Clinical Oncology 38, no. 15_suppl (2020): e15180-e15180. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e15180.

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e15180 Background: Double negative T cell (DNT) is defined by the expression of CD3 (or TCRαβ) with the absence of CD4, CD8 and iNKT cell markers. DNTs account for 1-3% of the total peripheral lymphocytes. Although healthy donor cells derived allogeneic DNTs were reported to have anti-tumor effects in several cancer models, the function of DNTs in tumor microenvironment is not well understood. In this study, we aim to characterize DNTs in cancer tissues and lymph nodes of colorectal cancer patients including their immunological functions. Methods: A total of 14 colorectal cancer tissues and re

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Santin, A. D., S. Bellone, M. Palmieri, et al. "Restoration of tumor specific human leukocyte antigens class I-restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer." International Journal of Gynecologic Cancer 14, no. 1 (2004): 64–75. http://dx.doi.org/10.1136/ijgc-00009577-200401000-00008.

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Despite the large number of potentially cytotoxic tumor-infiltrating (TIL) and tumor-associated (TAL) lymphocytes accumulated in the peritoneal cavity ascitic fluid and tumor tissue, advanced ovarian cancer is a progressive disease, suggesting that TIL and TAL populations eventually become functionally suppressed in vivo. Dendritic cells (DC) are the most powerful professional antigen presenting cells known in humans and recently, ovarian tumor antigen pulsed DC have been shown to elicit tumor specific human leukocyte antigens (HLA)-class I-restricted cytotoxicity from the peripheral blood of

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Diamanti, Paraskevi, Russell J. Garland, Derwood H. Pamphilon, Colin G. Steward, and Allison Blair. "Development of Clinical Scale Cytomegalovirus-Specific T Cells for Adoptive Immunotherapy Using pp65." Blood 106, no. 11 (2005): 5250. http://dx.doi.org/10.1182/blood.v106.11.5250.5250.

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Abstract Cytomegalovirus (CMV) represents a major cause of morbidity in patients undergoing allogeneic stem cell transplantation (SCT). Although antiviral prophylaxis has contributed to the reduction of early CMV disease, recovery of CMV-specific cytotoxic lymphocytes is still necessary for the long-term control of CMV reactivation after SCT. It has been demonstrated that CMV-specific CD4+ and CD8+ cytotoxic T lymphocytes from the donor are important in resolving CMV infection and protecting recipients from developing CMV disease post SCT. Recently CMV recombinant protein pp65, an immunodomina

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James, Edward, Jian-Guo Chai, Hamlata Dewchand, Eugenio Macchiarulo, Francesco Dazzi, and Elizabeth Simpson. "Multiparity induces priming to male-specific minor histocompatibility antigen, HY, in mice and humans." Blood 102, no. 1 (2003): 388–93. http://dx.doi.org/10.1182/blood-2002-10-3170.

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Abstract One of the factors that increases the risk of graft-versus-host disease following allogeneic stem cell transplantation is the use of multiparous females as donors. Since minor histocompatibility (H) antigens are the main targets of graft-versus-host and graft-versus-leukemia responses, we tested the hypothesis that multiparity could prime minor H antigen—specific T cells. We examined the peripheral lymphoid populations of multiparous mice and humans for evidence of priming of CD8+ T-cytotoxic lymphocytes against peptide epitopes of the male-specific minor H antigen, HY. In contrast to

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Lim, Alexander, Domenico Coppola, Young Doo Chang, Daniel A. Anaya, Dae Won Kim, and Richard D. Kim. "Relationship between tumor-infiltrating lymphocytes (TIL) and absolute lymphocyte count (ALC) or lymphocyte to neutrophil ratio (LTN) in cholangiocarcinoma (CCA)." Journal of Clinical Oncology 36, no. 4_suppl (2018): 343. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.343.

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343 Background: Tumor microenvironment is potentially a powerful predictive and prognostic marker of immunotherapy. The presence of CD8 TIL has been suggested as a predictive and prognostic marker of PD-1 inhibitor therapy in several malignancies. However, evaluation of TIL is not always feasible especially during or after immunotherapy. Therefore, easily accessible markers are needed for immune monitoring. In CCA, ALC and LTN in peripheral blood have been reported as prognostic factors. We evaluate the relationship between ALC or LTN and CD8 TILs in CCA. Methods: Formalin-fixed paraffin-embed

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Qian, Jianfei, Jin Xie, Sungyoul Hong, et al. "Dickkopf-1 (DKK1) is a widely expressed and potent tumor-associated antigen in multiple myeloma." Blood 110, no. 5 (2007): 1587–94. http://dx.doi.org/10.1182/blood-2007-03-082529.

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Abstract The identification of novel tumor-associated antigens, especially those shared among patients, is urgently needed to improve the efficacy of immunotherapy for multiple myeloma (MM). In this study, we examined whether Dickkopf-1 (DKK1), a protein that is not expressed in most normal tissues but is expressed by tumor cells from almost all patients with myeloma, could be a good candidate. We identified and synthesized DKK1 peptides for human leukocyte antigen (HLA)–A*0201 and confirmed their immunogenicity by in vivo immunization in HLA-A*0201 transgenic mice. We detected, using peptidet

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Sawamura, Yutaka, Hiroshi Abe, Toshimitsu Aida, Masuo Hosokawa, and Hiroshi Kobayashi. "Isolation and in vitro growth of glioma-infiltrating lymphocytes, and an analysis of their surface phenotypes." Journal of Neurosurgery 69, no. 5 (1988): 745–50. http://dx.doi.org/10.3171/jns.1988.69.5.0745.

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✓ The present investigation was conducted in order to examine the feasibility of isolating and growing gliomainfiltrating lymphocytes in vitro as possible effector cells for use in new adoptive immunotherapy. Eight surgical specimens obtained from patients with malignant astrocytomas were treated by enzyme dispersion; the cells were separated on a density gradient and grown in the presence of human recombinant interleukin-2. The cultured lymphocytes were tested for cell-surface markers by using monoclonal antibodies in a flow cytometric analysis. In all cases the glioma-derived lymphocytes wer

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Tseng, William W., Shruti Malu, Minying Zhang, et al. "Analysis of the Intratumoral Adaptive Immune Response in Well Differentiated and Dedifferentiated Retroperitoneal Liposarcoma." Sarcoma 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/547460.

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Treatment options are limited in well differentiated (WD) and dedifferentiated (DD) retroperitoneal liposarcoma. We sought to study the intratumoral adaptive immune response and explore the potential feasibility of immunotherapy in this disease. Tumor-infiltrating lymphocytes (TILs) were isolated from fresh surgical specimens and analyzed by flow cytometry for surface marker expression. Previously reported immune cell aggregates known as tertiary lymphoid structures (TLS) were further characterized by immunohistochemistry. In all fresh tumors, TILs were found. The majority of TILs were CD4 T c

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Ito, Yoshinori, Ayako Demachi-Okamura, Rieko Ohta, et al. "Full-length EBNA1 mRNA-transduced dendritic cells stimulate cytotoxic T lymphocytes recognizing a novel HLA-Cw*0303- and -Cw*0304-restricted epitope on EBNA1-expressing cells." Journal of General Virology 88, no. 3 (2007): 770–80. http://dx.doi.org/10.1099/vir.0.82519-0.

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Epstein–Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) is an attractive target for immunotherapy against EBV-associated malignancies because it is expressed in all EBV-positive cells. Although CD8+ cytotoxic T-lymphocyte (CTL) epitope presentation is largely prevented by its glycine–alanine-repeat domain (GAr), the use of mRNA-transduced dendritic cells (DCs) would offer the advantage of priming EBNA1-specific CTLs. After stimulation with GAr-containing EBNA1-transduced monocyte-derived DCs, two EBNA1-specific CTL clones, B5 and C6, were isolated successfully from a healthy donor. These CT

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Bocchialini, Giovanni, Costanza Lagrasta, Denise Madeddu, et al. "Spatial architecture of tumour-infiltrating lymphocytes as a prognostic parameter in resected non-small-cell lung cancer." European Journal of Cardio-Thoracic Surgery 58, no. 3 (2020): 619–28. http://dx.doi.org/10.1093/ejcts/ezaa098.

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Abstract OBJECTIVES Tumour-infiltrating lymphocytes (TILs) are critically implicated in the clinical outcome and response to immunotherapy in non-small-cell lung cancer (NSCLC) patients. The functional competence of lymphocyte subpopulations is strongly conditioned by their spatial arrangement within the tumour immune microenvironment. The aim of this study was to determine whether the tissue localization of specific TIL subpopulations might have an impact on the risk of recurrence in surgically resected NSCLC. METHODS High-speed scanning of whole slide images was performed on immunohistochemi

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Santin, Alessandro D., Paul L. Hermonat, Antonella Ravaggi, et al. "Induction of Human Papillomavirus-Specific CD4+ and CD8+ Lymphocytes by E7-Pulsed Autologous Dendritic Cells in Patients with Human Papillomavirus Type 16- and 18-Positive Cervical Cancer." Journal of Virology 73, no. 7 (1999): 5402–10. http://dx.doi.org/10.1128/jvi.73.7.5402-5410.1999.

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ABSTRACT Human papillomavirus (HPV) type 16 (HPV 16) and HPV type 18 (HPV 18) are implicated in the induction and progression of the majority of cervical cancers. Since the E6 and E7 oncoproteins of these viruses are expressed in these lesions, such proteins might be potential tumor-specific targets for immunotherapy. In this report, we demonstrate that recombinant, full-length E7-pulsed autologous dendritic cells (DC) can elicit a specific CD8+ cytotoxic T-lymphocyte (CTL) response against autologous tumor target cells in three patients with HPV 16- or HPV 18-positive cervical cancer. E7-spec

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Miyazaki, Yukihiro, Hiroshi Fujiwara, Toshiki Ochi, et al. "Human Telomerase Reverse Transcriptase-Specific T-Cell Receptor Gene Transfer Redirects T-Lymphocytes to Exert Effective Antitumor Reactivity Against Adult T-Cell Leukemia,." Blood 118, no. 21 (2011): 4169. http://dx.doi.org/10.1182/blood.v118.21.4169.4169.

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Abstract Abstract 4169 Background and Purpose Currently adult T-cell leukemia (ATL) is one of the most chemotherapy-resistant T cell malignancies and the prognosis of ATL patients still remains very poor. Although several novel treatment options, for example anti-chemokine receptor 4 (CCR4) monoclonal antibody, look promise, development of other novel treatment options still remains warranted. Currently activated status of human telomerase reverse transcriptase (hTERT) in ATL cells has been underscored. Thus, in this study, in order to develop a novel T cell-based immunotherapy for the treatme

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Dal Cortivo, Liliane, RITA Creidy, Aurélie Gabrion, et al. "Anti CMV and/or Anti Adenovirus IFN-g-Positive CD4+ CD8+ T Lymphocytes for Treatment of Viral Infections After Allogeneic HSC Transplantation: First Results." Blood 120, no. 21 (2012): 1906. http://dx.doi.org/10.1182/blood.v120.21.1906.1906.

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Abstract Abstract 1906 Reactivation of latent viruses such as cytomegalovirus (CMV) and adenovirus (AdV) is responsible for infections which may be life-threatening in HSCT recipients. In the post-transplantation period, severity and frequency of these infections depend on (a) the degree of donor-recipient HLA incompatibility and (b) the intensity of immunosuppressive therapy used to prevent immunological complications. Antiviral drugs may be partially effective, often toxic and cannot always control those viral infections.T cell immunity plays a major role in the control of viral infections.

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Riva, Giovanni, Mario Luppi, Patrizia Barozzi, et al. "Emergence of BCR-ABL–specific cytotoxic T cells in the bone marrow of patients with Ph+ acute lymphoblastic leukemia during long-term imatinib mesylate treatment." Blood 115, no. 8 (2010): 1512–18. http://dx.doi.org/10.1182/blood-2009-06-230391.

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Abstract Imatinib mesylate has been demonstrated to allow the emergence of T cells directed against chronic myeloid leukemia cells. A total of 10 Philadelphia chromosome–positive acute lymphoblastic leukemia patients receiving high-dose imatinib mesylate maintenance underwent long-term immunological monitoring (range, 2-65 months) of p190BCR-ABL–specific T cells in the bone marrow and peripheral blood. p190BCR-ABL–specific T lymphocytes were detected in all patients, more frequently in bone marrow than in peripheral blood samples (67% vs 25%, P < .01) and resulted significantly associated w

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Shaffer, Donald, Barbara Savoldo, Gianpietro Dotti, et al. "T-Cells Redirected Against CD70 for the Immunotherapy of Hematological Malignancies." Blood 110, no. 11 (2007): 2757. http://dx.doi.org/10.1182/blood.v110.11.2757.2757.

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Abstract BACKGROUND: CD70 is a tumor necrosis family member that is expressed on a broad spectrum of hematological malignancies including multiple myeloma, non-Hodgkin’s lymphomas and Hodgkin’s disease. In contrast to other already established immunotherapy targets such as CD19, CD20, or CD52, which are widely expressed in the hematopoietic system, CD70 expression is restricted to a subset of activated B and T cells, reducing potential ‘collateral damage’ when targeted by immunotherapy. Preclinical studies in animal models using monoclonal antibodies have validated CD70 as an immunotherapeutic

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Kim, Byung-Seok, Da-Sol Kuen, Choong-Hyun Koh, et al. "Type 17 immunity promotes the exhaustion of CD8+ T cells in cancer." Journal for ImmunoTherapy of Cancer 9, no. 6 (2021): e002603. http://dx.doi.org/10.1136/jitc-2021-002603.

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BackgroundMultiple types of immune cells producing IL-17 are found in the tumor microenvironment. However, their roles in tumor progression and exhaustion of CD8+ tumor-infiltrating lymphocytes (TILs) remain unclear.MethodsTo determine the role of type 17 immunity in tumor, we investigated the growth of B16F10 melanoma and the exhaustion of CD8+ TILs in Il17a−/− mice, Il17aCreR26DTA mice, RORγt inhibitor-treated mice, or their respective control mice. Adoptive transfer of tumor-specific IL-17-producing T cells was performed in B16F10-bearing congenic mice. Anti-CD4 or anti-Ly6G antibodies were

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Ochi, Toshiki, Hiroshi Fujiwara, Kozo Nagai, et al. "Development of Novel Stem Cell Transplantation and Gene-Immunotherapy Using WT1-Specific T-Cell Receptor Gene." Blood 114, no. 22 (2009): 3028. http://dx.doi.org/10.1182/blood.v114.22.3028.3028.

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Abstract Abstract 3028 Poster Board II-1004 Purpose The Wilms' tumor 1 (WT1) is one of the zinc-finger transcriptional regulators, and its expression level is very low in most tissues of adults. In contrast, various kinds of leukemia and solid tumors express WT1 abundantly, and high expression level of WT1 is correlated with disease aggressiveness and poor prognosis. These findings indicate that WT1 is a promising target antigen for anti-cancer cellular immunotherapy. Following identification of immunogenic epitopes derived from WT1 which are recognized by HLA class I-restricted and HLA class

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Ogasawara, Masahiro, Tomohiro Yamakawa, Yuki Katsura, et al. "Efficient Generation of HLA-A24-Restricted WT1-Specific Cytotoxic T Lymphocytes Using Gene-Engineered Artificial Antigen-Presenting Cells." Blood 116, no. 21 (2010): 2101. http://dx.doi.org/10.1182/blood.v116.21.2101.2101.

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Abstract Abstract 2101 Background and Purpose: Recent success associated with adoptive transfer of antitumor T cells in lymphodepleted patients suggests the potential of adoptive immunotherapy to have a significant clinical impact. However, the widespread use of adoptive therapy has been hampered by the difficulty of consistently generating potent antitumor lymphocytes in a timely manner for every patient. To overcome this, we previously reported a culture system that can reproducibly generate antigen-specific cytotoxic T lymphocytes (CTL) from HLA-A2-positive melanoma patients by using K562-b

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Lagos, Galina, Roman Groisberg, Don S. Dizon, et al. "Large scale multiomic analysis suggests mechanisms of resistance to immunotherapy in leiomyosarcoma." Journal of Clinical Oncology 39, no. 15_suppl (2021): 11512. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.11512.

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11512 Background: Leiomyosarcomas (LMS) have been reported to have immunohistochemical (IHC) and gene expression signatures suggestive of an immune-responsive tumor microenvironment. Despite this, immune checkpoint inhibitors have demonstrated minimal activity in LMS. We examined molecular profiles of LMS specimens from multiple institutions to explore mechanisms of immunotherapy (IO) resistance. Methods: LMS specimens (n = 1115), including 701 uterine (uLMS) and 414 soft tissue site (stLMS) samples, underwent next-generation sequencing (NGS) of DNA (592-gene panel or whole exome) and RNA (who

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Rocha, Marian, Victor Umansky, Kyeong-Hee Lee, Hans-Jörg Hacker, Axel Benner, and Volker Schirrmacher. "Differences Between Graft-Versus-Leukemia and Graft-Versus-Host Reactivity. I. Interaction of Donor Immune T Cells With Tumor and/or Host Cells." Blood 89, no. 6 (1997): 2189–202. http://dx.doi.org/10.1182/blood.v89.6.2189.

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Abstract Graft-versus-leukemia (GVL) and Graft-versus-host (GVH) reactions were compared after systemic transfer of allogeneic antitumor immune T lymphocytes from B10.D2 (H-2d; MIsb) into DBA/2 (H-2d; MIsa) mice. Before immune cell transfer, recipient DBA/2 mice were sublethally irradiated with 5 Gy to prevent host-versus-graft reactivity. Recipients were either bearing syngeneic metastatic ESb lymphomas (GVL system) or were normal, non–tumor-bearing mice (GVH system). We previously reported that this adoptive immunotherapy protocol (ADI) had pronounced GVL activity and led to immune rejection

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Kaur, K., V. Suri, M. C. Sharma, A. Garg, A. Suri, and C. Sarkar. "P04.19 Analysis of tumor immune microenvironment and immune checkpoint modulators across infantile and pediatric pilocytic astrocytomas to elucidate the role of immunotherapy in these tumors." Neuro-Oncology 21, Supplement_3 (2019): iii33. http://dx.doi.org/10.1093/neuonc/noz126.114.

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Abstract BACKGROUND Pilocytic astrocytomas are the most common central nervous system tumors in pediatric age-group. Although grade I, some of the cases show recurrence and progression, and few might not be amenable to surgery due to location or size, and hence have a less favorable prognosis. Drugs blocking immune check-point interactions such as those including programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are now in clinical use for certain tumors. We performed this study to understand the potential candidature of pilocytic astrocytomas in i

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Urbaniak-Kujda, Donata, Jaroslaw Dybko, Iwona Prajs, et al. "Is CD94/NKG2A a Novel Target for Lymphoid Malignancies Immunotherapy?." Blood 108, no. 11 (2006): 4650. http://dx.doi.org/10.1182/blood.v108.11.4650.4650.

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Abstract Background: Natural killer (NK)-cell receptors (NKRs) on CD8+ T cells can modulate antigen-specific T cell activity but their function and rules that govern their expression remain unclear. Among NKRs heterodimers CD94-NKG2 form either an inhibitory or an activating receptor, depending on whether CD94 associates with NKG2A or NKG2C, E or H, respectively. NKG2D is expressed on all naïve and activated CD8+ T cells. NKG2D ligands are distantly related to HLA class I molecules and up-regulated in virally infected cells, tumour cells or otherwise stressed cells. The expression of NKG2D li

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Liu, Hongwei, Bill H. Wu, Gerry J. Rowse, and Peter C. R. Emtage. "Induction of CD4-Independent E7-Specific CD8+ Memory Response by Heat Shock Fusion Protein." Clinical and Vaccine Immunology 14, no. 8 (2007): 1013–23. http://dx.doi.org/10.1128/cvi.00029-07.

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ABSTRACT Infection with human papillomavirus type 16 (HPV16) is strongly associated with a number of disease states, of which cervical and anal cancers represent the most drastic endpoints. Induction of T-cell-mediated immunity, particularly cytotoxic T lymphocytes (CTL), is important in eradication of HPV-induced lesions. Studies have shown that heat shock protein fusion proteins are capable of inducing potent antigen-specific CTL activity in experimental animal models. In addition, E7-expressing tumors in C57BL/6 mice can be eradicated by treatment with HspE7, an Hsp fusion protein composed

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Dander, Erica, Giuseppina Li Pira, Ettore Biagi, Fabrizio Manca, Andrea Biondi, and Giovanna D’Amico. "Generation of Cytomegalovirus (CMV)-Specific CD4 and CD8 T Cell Lines Using Protein-Spanning Pools of pp65 and IE1 Derived Peptides." Blood 106, no. 11 (2005): 477. http://dx.doi.org/10.1182/blood.v106.11.477.477.

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Abstract BACKGROUND: Reactivation of latent CMV in immunocompromised recipients of allogeneic stem cell transplantation remains a major cause of morbidity and mortality. Reconstitution of immunity by CMV specific immunotherapy is an attractive alternative to drugs currently used, which show high toxicity and are sometimes ineffective. It has been demonstrated that CD4 helper T-cell function is crucial for the persistence of in vivo transferred CD8 CMV-specific CTL. Based on this finding, we have explored the feasibility of generating both anti-CMV CD4 and anti-CMV CD8 T-cell lines. METHODS: De

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Ademuyiwa, Foluso Olabisi, Wiam Bshara, Kristopher Attwood, et al. "Immunogenicity of NY-ESO-1 cancer testis antigen in triple-negative breast cancer." Journal of Clinical Oncology 30, no. 15_suppl (2012): e11563-e11563. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e11563.

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e11563 Background: NY-ESO-1 cancer testis (CT) antigen is an attractive candidate for immunotherapy as a result of its high immunogenicity. The aim of this study was to explore the potential for NY-ESO-1 antigen directed immunotherapy in triple negative breast cancer (TNBC) by determining the frequency of expression by immunohistochemistry (IHC) and the degree of inherent immunogenicity to NY-ESO-1. Methods: 168 TNBC and 47 ER+/HER2- primary breast cancer specimens were used to determine NY-ESO-1 frequency by IHC. As previous studies have shown that patients with a robust innate humoral immune

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Fujiwara, Hiroshi, Frank El Ouriaghli, Matthias Grube, et al. "Identification and in vitro expansion of CD4+ and CD8+ T cells specific for human neutrophil elastase." Blood 103, no. 8 (2004): 3076–83. http://dx.doi.org/10.1182/blood-2003-07-2424.

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Abstract Human neutrophil elastase (HNE) and proteinase 3 (PRO3) are myeloid tissue-restricted serine proteases, aberrantly expressed by myeloid leukemia cells. PRO3 and HNE share the PR1 peptide sequence that induces HLA-A*0201–restricted cytotoxic T cells (CTLs) with antileukemia reactivity. We studied the entire HNE protein for its ability to induce CTLs. In an 18-hour culture, HNE-loaded monocytes stimulated significant intracellular interferon γ (IFN-γ) production by CD4+ and CD8+ T cells in 12 of 20 and 8 of 20 healthy individuals, respectively. Lymphocytes from 2 HNE responders were pul

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Nagamura-Inoue, Tokiko, Atsuko Takahashi, Yuki Yamamoto, et al. "Immunosuppressive Diversity of Umbilical Cord-Derived Mesenchymal Stromal Cells." Blood 134, Supplement_1 (2019): 3584. http://dx.doi.org/10.1182/blood-2019-128627.

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Recently, umbilical cord (UC) has become attracted source of mesenchymal stromal cells (MSCs) for immunotherapy such as treatment of severe acute graft versus host disease, because of abundant sources and ease of collection without invasive process. In previous reports on bone marrow-derived MSCs, there is diversity of immunosuppressive mechanisms of MSCs, which have not yet fully clarified in UC-MSCs. Here we studied the immunosuppressive properties of UC-MSCs on the activated immune system in vitro. Methods; UC was collected after obtaining informed consent from the mother. UC-MSCs were obta

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Zou, Yutian, Xuxiazi Zou, Shaoquan Zheng, et al. "Efficacy and predictive factors of immune checkpoint inhibitors in metastatic breast cancer: a systematic review and meta-analysis." Therapeutic Advances in Medical Oncology 12 (January 2020): 175883592094092. http://dx.doi.org/10.1177/1758835920940928.

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Background: Immune checkpoint inhibitors (ICIs) have shown encouraging treatment efficacy for metastatic breast cancer in several clinical trials. However, response only occurred in a small population. Evidence predicting response and survival of patients with metastatic breast cancer following ICI treatment with existing biomarkers has not been well summarized. This review aimed to summarize the efficacy and predictive factors of immune checkpoint therapy in metastatic breast cancer, which is critical for clinical practice. Methods: PubMed, Embase, Cochrane Library, Web of Science, www.clinic

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Gao, Qiang, Shuang-Jian Qiu, Jia Fan, et al. "Intratumoral Balance of Regulatory and Cytotoxic T Cells Is Associated With Prognosis of Hepatocellular Carcinoma After Resection." Journal of Clinical Oncology 25, no. 18 (2007): 2586–93. http://dx.doi.org/10.1200/jco.2006.09.4565.

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Purpose To investigate the prognostic value of tumor-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in hepatocellular carcinoma (HCC) patients after resection. Patients and Methods CD3+, CD4+, CD8+, Foxp3-positive, and granzyme B-positive TILs were assessed by immunohistochemistry in tissue microarrays containing HCC from 302 patients. Prognostic effects of low- or high-density TIL subsets were evaluated by Cox regression and Kaplan-Meier analysis using median values as cutoff. Results CD3+, CD4+, CD8+ TILs were associated with neither overall survival (OS) nor disease

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Schilbach, Karin, Gunter Kerst, Steffen Walter, et al. "Cytotoxic minor histocompatibility antigen HA-1–specific CD8+ effector memory T cells: artificial APCs pave the way for clinical application by potent primary in vitro induction." Blood 106, no. 1 (2005): 144–49. http://dx.doi.org/10.1182/blood-2004-07-2940.

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Induction of cytotoxic T lymphocytes (CTLs) for treatment of relapsed leukemia after allogeneic stem-cell transplantation is hindered by the laborious and time-consuming procedure of generating dendritic cells for antigen presentation. Artificial antigen-presenting cells (aAPCs) offer the advantage of being readily available in sufficient numbers, thus allowing for a highly standardized in vitro induction of CTLs. We generated aAPCs coated with anti-CD28 antibody (Ab) and either high-density (HD) or low-density (LD) major histocompatibility complex (MHC) class I molecules loaded with HA-1H, a

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Burchielli, Emanuela, Antonella Tosti, Loredana Ruggeri, Katia Perruccio, Claudia De Angelis, and Andrea Velardi. "Adoptive Therapy with T-Cell Precursors for Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation." Blood 114, no. 22 (2009): 3525. http://dx.doi.org/10.1182/blood.v114.22.3525.3525.

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Abstract Abstract 3525 Poster Board III-462 Recipients of allogeneic hematopoietic transplantation experience a slow reconstitution of donor-derived B and T cell number and function. This post-transplant period of immunodeficiency is associated with an increased risk of infection and malignant relapse. The developement of these complications notably correlates with the recovery of CD4+T cell subset. We proposed a strategy to enhances in vivo reconstitution by promoting donor-derived T cell development in the recipient's thymus. Recently Notch1-based ex-vivo system have been established to matu

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Ranieri, E., W. Herr, A. Gambotto, et al. "Dendritic Cells Transduced with an Adenovirus Vector Encoding Epstein-Barr Virus Latent Membrane Protein 2B: a New Modality for Vaccination." Journal of Virology 73, no. 12 (1999): 10416–25. http://dx.doi.org/10.1128/jvi.73.12.10416-10425.1999.

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ABSTRACT Epstein-Barr virus (EBV) is a herpesvirus commonly associated with several malignancies, particularly in immunocompromised hosts. As a strategy for stimulating immunity against EBV for the treatment of EBV-associated tumors, we have genetically engineered dendritic cells (DC) to express EBV antigens, such as latent membrane protein 2B (LMP2B), using recombinant adenovirus vectors. CD8+ T lymphocytes from HLA-A2.1+, EBV-seropositive healthy donors were cultured with autologous DC infected with recombinant adenovirus vector AdEGFP, encoding an enhanced green fluorescent protein (EGFP),

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Kunk, Paul Raymond, Joseph Mounir Obeid, Kevin Winters, et al. "Correlation of mesothelin expression and CD8 tumor infiltrating lymphocytes with prognosis in cholangiocarcinoma." Journal of Clinical Oncology 35, no. 15_suppl (2017): e15650-e15650. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e15650.

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e15650 Background: Cholangiocarcinoma (CC) is a rapidly progressing malignancy with an unmet treatment need. Little is known about the CC tumor immune microenvironment or about relevant antigenic targets. We hypothesized that lack of T cell infiltration or PD-L1 expression may identify patients at high risk of death, and that mesothelin may be a relevant antigenic target. Methods: A retrospective analysis was conducted of CC tumors at the University of Virginia from 2000-2014. TMAs were constructed of 3-4 cores from each tumor and were stained by IHC for CD4 and CD8 tumor infiltrating lymphocy

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Borobova, E. A., D. V. Antonets, E. V. Starostina, et al. "Ability of protein epitope-containing constructs associated with melanoma to stimulate the cytotoxic activity of peripheral blood mononuclear cells against melanoma cells." Siberian journal of oncology 18, no. 1 (2019): 43–49. http://dx.doi.org/10.21294/1814-4861-2019-18-1-43-49.

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Aim. The aim of the study was to evaluate the ability of pMEL-TCI and pMEL-A0201 DNA-constructs encoding artificial polyepitope melanoma antigens to induce antitumor T cell immune response ex vivo. material and methods. Dendritic cells were obtained from peripheral blood mononuclear cells of HLA-A02:01-positive donors; DCs transfected with target DNA vaccine constructions were co-cultured with autologous T lymphocytes to stimulate anti-tumor effector T cells. Specific activity of ex vivo stimulated PBMC was assessed (1) by their ability to cause lysis of human melanoma Mel Is cells, and (2) by

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Cieremans, David, Ju Young Kim, Ariana Valencia, et al. "BIOM-27. PREDICTIVE EVALUATION OF QUANTITATIVE SPATIAL PROFILING OF THE TUMOR MICROENVIRONMENT BY MULTIPLEX IMMUNOFLUORESCENCE IN RECURRENT GLIOBLASTOMA TREATED WITH PD-1 INHIBITORS." Neuro-Oncology 22, Supplement_2 (2020): ii7. http://dx.doi.org/10.1093/neuonc/noaa215.027.

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Abstract BACKGROUND PD-1 inhibitors have shown limited efficacy in glioblastoma (GBM) due to microenvironment immunosuppression and low tumor mutational burden. In GBM, PD-L1 expression is not a predictive marker for response to PD-1 or PD-L1 inhibitors. Multiplex immunostaining panel technology allows for detailed analyses of tumor microenvironment cells and their interaction. METHODS Pre-treatment tumor tissue was collected retrospectively from 27 patients in our neurooncology database at Columbia University Irving Medical Center with primary glioblastoma who were diagnosed within the past t

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Malone, Eoghan Ruadh, Nathaniel Anderson, Jeremy Howard Lewin, et al. "Immune signature and molecular profiling of radiation-induced sarcoma (RIS)." Journal of Clinical Oncology 37, no. 15_suppl (2019): 11040. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.11040.

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11040 Background: RIS is a rare subset of soft tissue sarcoma (STS) with poor prognosis and limited treatment options. We hypothesize that subsets of STS that carry genomic complexity, such as RIS, will have a neoepitope and immune signature that predicts response to immunotherapy as these mutations act as strong antigenic targets for eliciting immune response. Methods: Cases of RIS were identified from an institutional database. Formalin fixed paraffin embedded (FFPE) samples were stained for PD-1, PD-L1, CD3, CD4, CD8. Immune scoring was performed. Tumor-infiltrating lymphocytes (TILs) were

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Orlowski, Robert, Alexander Huang, Mercy Gohil, et al. "Integrated Immunological Analysis of the Bone Marrow Tumor Microenvironment in Myeloproliferative Neoplasms to Determine Potential Efficacy of Immune Checkpoint Blockade." Blood 126, no. 23 (2015): 2766. http://dx.doi.org/10.1182/blood.v126.23.2766.2766.

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Abstract BACKGROUND: Immune checkpoint blockadewith anti-PD-1/PD-L1 therapyhas demonstrated remarkable efficacy in multiple tumor types. Biomarker candidates for predicting likelihood of response to targeted immunotherapy are being actively investigated including inhibitory or activating receptors on CD8+ lymphocytes, corresponding ligands on tumor or antigen-presenting cells (APCs), T-cell functionality, and the T-cell receptor (TCR) repertoire found within a tumor microenvironment. Myelofibrosis (MF) and Chronic Myeloid Leukemia (CML) are tumors responsive to immunotherapy, most notably allo

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