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Journal articles on the topic 'Agnostic antibody'

Author: Grafiati

Published: 4 June 2025

Last updated: 1 August 2025

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1

van Vloten, Jacob P., Elaine M. Klafuric, Khalil Karimi, et al. "Quantifying Antibody Responses Induced by Antigen-Agnostic Immunotherapies." Molecular Therapy - Methods & Clinical Development 14 (September 2019): 189–96. http://dx.doi.org/10.1016/j.omtm.2019.06.010.

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Dias e Silva, Douglas, Guilherme Malandrini Andriatte, and Roberto Carmagnani Pestana. "Antibody-Drug Conjugates and Tissue-Agnostic Drug Development." Cancer Journal 28, no. 6 (2022): 462–68. http://dx.doi.org/10.1097/ppo.0000000000000633.

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Thein, Kyaw Z., Yin M. Myat, Byung S. Park, Kalpana Panigrahi, and Shivaani Kummar. "Target-Driven Tissue-Agnostic Drug Approvals—A New Path of Drug Development." Cancers 16, no. 14 (2024): 2529. http://dx.doi.org/10.3390/cancers16142529.

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The regulatory approvals of tumor-agnostic therapies have led to the re-evaluation of the drug development process. The conventional models of drug development are histology-based. On the other hand, the tumor-agnostic drug development of a new drug (or combination) focuses on targeting a common genomic biomarker in multiple cancers, regardless of histology. The basket-like clinical trials with multiple cohorts allow clinicians to evaluate pan-cancer efficacy and toxicity. There are currently eight tumor agnostic approvals granted by the Food and Drug Administration (FDA). This includes two im

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Abelman, R., L. M. Spring, R. Corcoran, and A. Bardia. "Moving towards tissue-agnostic antibody drug conjugates: HER2 expression as the poster child." Annals of Oncology 34, no. 11 (2023): 968–69. http://dx.doi.org/10.1016/j.annonc.2023.10.115.

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5

Chin, Amanda, Rubin Jiao, Kevin J. H. Allen, et al. "Lintuzumab-Ac225, a CD33-Directed Antibody Radiotherapy, Targets AML in a Mutation Agnostic Manner." Blood 142, Supplement 1 (2023): 5750. http://dx.doi.org/10.1182/blood-2023-187498.

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Introduction Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy with a poor survival prognosis. Recurrent gene mutations are the major obstacle that impact treatment efficacy of AML patients. Actimab-A, an anti-CD33 antibody conjugated with Actinium-225 (Ac-225) alpha particle-emitting radionuclide (lintuzumab-Ac225), has demonstrated promising therapeutic responses in AML patients, including in combination trials with chemotherapy regimen CLAG-M and targeted therapy venetoclax. Because lintuzumab-Ac225 broadly targets myeloid cells via CD33, we hypothesized that ant

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Savard, Marie-France, Omar Khan, Kelly K. Hunt, and Sunil Verma. "Redrawing the Lines: The Next Generation of Treatment in Metastatic Breast Cancer." American Society of Clinical Oncology Educational Book, no. 39 (May 2019): e8-e21. http://dx.doi.org/10.1200/edbk_237419.

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Although not considered curative in nature, new therapeutic advances in metastatic breast cancer (MBC) have substantially improved patient outcomes. This article discusses the state-of-the-art and emerging therapeutic options for management of MBC. BC systemic therapy targets multiple key pathways, including estrogen receptor signaling, HER2 signaling, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling. Other therapeutic strategies include targeting DNA repair, inhibiting immune checkpoints, and developing antibody-drug conjugates. Althou

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Zhang, Ruijun, Ponraj Prabakaran, Xiaocong Yu, et al. "A platform-agnostic, function first-based antibody discovery strategy using plasmid-free mammalian expression of antibodies." mAbs 13, no. 1 (2021): 1904546. http://dx.doi.org/10.1080/19420862.2021.1904546.

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Lanzavecchia, Antonio. "Dissecting Human Antibody Responses: Useful, Basic, and Surprising Findings." Blood 130, Suppl_1 (2017): SCI—49—SCI—49. http://dx.doi.org/10.1182/blood.v130.suppl_1.sci-49.sci-49.

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Abstract We use cell culture-based high-throughput methods to interrogate human memory B cell and plasma cell repertoires and to isolate antibodies selected on the basis of their neutralizing potency and breadth. Relevant examples are antibodies that neutralize all influenza A viruses or even four paramyxoviruses. By targeting conserved structures, these broadly neutralizing antibodies are less prone to select escape mutants and are promising candidates for prophylaxis and therapy of infections, as well as tools for vaccine design. The value of a target-agnostic approach to vaccine design is i

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Hong, Wan Xing, Idit Sagiv-Barfi, Debra K. Czerwinski, Adrienne Sallets, and Ronald Levy. "Neoadjuvant Intratumoral Immunotherapy with TLR9 Activation and Anti-OX40 Antibody Eradicates Metastatic Cancer." Cancer Research 82, no. 7 (2022): 1396–408. http://dx.doi.org/10.1158/0008-5472.can-21-1382.

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Abstract The combination of the synthetic TLR9 ligand CpG and agnostic OX40 antibody can trigger systemic antitumor immune responses upon co-injection into the tumor microenvironment, eradicating simultaneous untreated sites of metastatic disease. Here we explore the application of this in situ immunotherapy to the neoadjuvant setting. Current neoadjuvant checkpoint blockade therapy is delivered systemically, resulting in off-target adverse effects. In contrast, intratumoral immunotherapy minimizes the potential for toxicities and allows for greater development of combination therapies. In two

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Kok, Marleen, Myriam Chalabi, and John Haanen. "How I treat MSI cancers with advanced disease." ESMO Open 4, Suppl 2 (2019): e000511. http://dx.doi.org/10.1136/esmoopen-2019-000511.

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Mismatch repair deficiency (dMMR) results in microsatellite instability (MSI) and is strongly associated with responsiveness to programmed death-1 receptor (PD-1)-blocking antibodies. Probably the main driver for the observed high efficacy of immune checkpoint inhibitors in dMMR tumours is the remarkably high tumour mutational burden. MSI can be detected using immunohistochemistry and/or PCR. In addition, next-generation sequencing is becoming increasingly available to clinical laboratories as a cost-effective and scalable method to evaluate multiple genetic aberrations including MSI. Efficacy

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Mishra, Avanish, Taronish D. Dubash, Jon F. Edd, et al. "Ultrahigh-throughput magnetic sorting of large blood volumes for epitope-agnostic isolation of circulating tumor cells." Proceedings of the National Academy of Sciences 117, no. 29 (2020): 16839–47. http://dx.doi.org/10.1073/pnas.2006388117.

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Circulating tumor cell (CTC)-based liquid biopsies provide unique opportunities for cancer diagnostics, treatment selection, and response monitoring, but even with advanced microfluidic technologies for rare cell detection the very low number of CTCs in standard 10-mL peripheral blood samples limits their clinical utility. Clinical leukapheresis can concentrate mononuclear cells from almost the entire blood volume, but such large numbers and concentrations of cells are incompatible with current rare cell enrichment technologies. Here, we describe an ultrahigh-throughput microfluidic chip,LPCTC

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Momin, Noor, Naveen K. Mehta, Nitasha R. Bennett, et al. "Anchoring of intratumorally administered cytokines to collagen safely potentiates systemic cancer immunotherapy." Science Translational Medicine 11, no. 498 (2019): eaaw2614. http://dx.doi.org/10.1126/scitranslmed.aaw2614.

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The clinical application of cytokine therapies for cancer treatment remains limited due to severe adverse reactions and insufficient therapeutic effects. Although cytokine localization by intratumoral administration could address both issues, the rapid escape of soluble cytokines from the tumor invariably subverts this effort. We find that intratumoral administration of a cytokine fused to the collagen-binding protein lumican prolongs local retention and markedly reduces systemic exposure. Combining local administration of lumican-cytokine fusions with systemic immunotherapies (tumor-targeting

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Lee, Saehyung, Jae Choi, Sunghyun Hong, et al. "Abstract 2653: ABN501, a novel anti-claudin-3 antibody, shows potent anti-cancer activity in vitro and in vivo." Cancer Research 83, no. 7_Supplement (2023): 2653. http://dx.doi.org/10.1158/1538-7445.am2023-2653.

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Abstract Claudin-3, one of the tight junction proteins, could be a potential therapeutic target and biomarker. Since it is not only overexpressed in various types of malignant solid cancers but also exposed externally during tumorigenesis. Previously, we developed a fully human monoclonal antibody (ABN501) with sub-nanomolar affinity against the native claudin-3 protein. In this study, we confirmed that ABN501 is highly specific for the extracellular loop (ECL) 2 domain of claudin-3 using stable cell lines expressing two chimeric claudins fused to claudin-3 and claudin-4. Followed by, we evalu

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Groen, Aaron C., Nisha Shrestha, Boris Klebanov, et al. "Abstract 7209: Status-agnostic therapy of breast cancer using antibodies targeting O-glycosylated proteins." Cancer Research 85, no. 8_Supplement_1 (2025): 7209. https://doi.org/10.1158/1538-7445.am2025-7209.

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Abstract We have developed a novel antibody-drug conjugate (ADC), based on the mAb L100, that selectively targets a O-GalNAc-glycoprotein expressed in approximately 20% of all breast cancer. Unlike many ADC programs targeting Breast Cancer, L100 recognizes cancer-specific O-glycosylated versions of proteins do not present on normal tissues circumventing adverse events from on target off tumor binding to healthy tissues. The crystal structure of L100 provides insights into its binding specificity and affinity. L100 exhibits low nanomolar affinity (0.83nM) to the glycoprotein target and has also

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Ramasamy, Santhamani, Abhinay Gontu, Sabarinath Neerukonda, et al. "SARS-CoV-2 Prevalence and Variant Surveillance among Cats in Pittsburgh, Pennsylvania, USA." Viruses 15, no. 7 (2023): 1493. http://dx.doi.org/10.3390/v15071493.

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects many mammals, and SARS-CoV-2 circulation in nonhuman animals may increase the risk of novel variant emergence. Cats are highly susceptible to SARS-CoV-2 infection, and there were cases of virus transmission between cats and humans. The objective of this study was to assess the prevalence of SARS-CoV-2 variant infection of cats in an urban setting. We investigated the prevalence of SARS-CoV-2 variant infections in domestic and community cats in the city of Pittsburgh (n = 272). While no cats tested positive for SARS-CoV-2 vira

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Chin, Amanda, Rubin Jiao, Kevin J. H. Allen, et al. "Lintuzumab-Ac225 Exerts Mutation Agnostic Antileukemic Activity in Preclinical Models of AML." Blood 144, Supplement 1 (2024): 5801. https://doi.org/10.1182/blood-2024-204282.

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Introduction Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy with a poor survival prognosis. Genetic aberrations are drivers of leukemogenesis and can negatively impact treatment efficacy and durability of responses in patients, with most relapsing following treatment with small molecule inhibitors and/or standard-of-care chemotherapy. We have shown that myeloid leukemic cells are broadly targeted by lintuzumab-Ac225, a CD33-directed monoclonal antibody conjugated with the alpha particle-emitting radionuclide actinium-225. In clinical trials, lintuzumab-Ac225 has

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Nguyen, Liem, Chun-Shu Wong, Serena Wo, et al. "Abstract 2355: SGN-EGFRd2 binding and activity are agnostic to common EGFR extracellular resistance mutations acquired in response to anti-EGFR targeted antibody therapies." Cancer Research 84, no. 6_Supplement (2024): 2355. http://dx.doi.org/10.1158/1538-7445.am2024-2355.

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Abstract SGN-EGFRd2 is an investigational bispecific antibody comprised of two camelid-derived humanized variable heavy chain only (VHH) domains, one targeting Vγ9Vδ2 (gamma delta) T cells and the other targeting the epidermal growth factor receptor (EGFR). Selective antitumor activity occurs when two conditions are met: 1) the molecule engages both EGFR-expressing tumor cells and gamma delta T cells and 2) butyrophilins, in complex with phosphoantigens (pAgs), are expressed by EGFR-positive tumor cells, resulting in gamma delta T cell directed tumor cell killing by activation, degranulation a

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Xavier, Camila B., Carlos Diego H. Lopes, Beatriz M. Awni, et al. "Interplay between Tumor Mutational Burden and Mutational Profile and Its Effect on Overall Survival: A Pilot Study of Metastatic Patients Treated with Immune Checkpoint Inhibitors." Cancers 14, no. 21 (2022): 5433. http://dx.doi.org/10.3390/cancers14215433.

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Purpose: Solid tumors harboring tumor mutational burden (TMB) ≥10 mutations per megabase (mut/Mb) received agnostic approval for pembrolizumab. This work aims to analyze the somatic mutational profile’s influence on the outcomes of patients with TMB-high tumors treated with immune checkpoint inhibitors (ICIs). Methods: This post-hoc analysis evaluated clinical and molecular features of patients with solid tumors treated with ICIs that could be either monoclonal antibody directed against programmed cell death protein-1 or monoclonal antibody directed against programmed cell death ligand 1 (anti

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Nakano, Kenji. "The Future of HER2-Targeted Treatment for Osteosarcoma: Lessons from the Negative Trastuzumab Deruxtecan Results." International Journal of Molecular Sciences 24, no. 23 (2023): 16823. http://dx.doi.org/10.3390/ijms242316823.

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Human epidermal growth factor receptor 2 (HER2), coded by the proto-oncogene ERBB, is known to be mutated or amplified in various malignant diseases, and many HER2-targeted therapies (including monoclonal antibodies and low-molecular-weight tyrosine kinase inhibitors) have been investigated. HER2 overexpression is observed in ~30% of patients with osteosarcoma, and HER2-targeted therapy for osteosarcoma has also been investigated, along with the prognostic and/or predictive value of HER2. An effective HER2-targeted therapy for osteosarcoma has not been established, however. An antibody–drug co

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Iacobucci, Ilaria, Shunsuke Kimura, and Charles G. Mullighan. "Biologic and Therapeutic Implications of Genomic Alterations in Acute Lymphoblastic Leukemia." Journal of Clinical Medicine 10, no. 17 (2021): 3792. http://dx.doi.org/10.3390/jcm10173792.

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Acute lymphoblastic leukemia (ALL) is the most successful paradigm of how risk-adapted therapy and detailed understanding of the genetic alterations driving leukemogenesis and therapeutic response may dramatically improve treatment outcomes, with cure rates now exceeding 90% in children. However, ALL still represents a leading cause of cancer-related death in the young, and the outcome for older adolescents and young adults with ALL remains poor. In the past decade, next generation sequencing has enabled critical advances in our understanding of leukemogenesis. These include the identification

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Chin, Amanda S., Rubin Jiao, Kevin J. Allen, et al. "Abstract 594: Lintuzumab-Ac225 has potent mutation agnostic antileukemic activity in preclinical models of AML." Cancer Research 85, no. 8_Supplement_1 (2025): 594. https://doi.org/10.1158/1538-7445.am2025-594.

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Abstract Introduction: Acute myeloid leukemia (AML) is a complex and aggressive blood cancer with a poor prognosis, driven by genetic mutations that complicate treatment and often lead to relapse. Lintuzumab-Ac225 is a promising investigational antibody radio-conjugate that targets CD33. The payload, actinium-225 (Ac-225) is an alpha particle-emitting radionuclide that causes lethal DNA damage. In clinical trials, lintuzumab-Ac225 had positive responses when combined with CLAG-M chemotherapy in relapsed/refractory AML patients, including those with high-risk features like venetoclax resistance

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Gilbert, Lucy, Ana Oaknin, Ursula A. Matulonis та ін. "Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-agnostic ovarian cancer." Journal of Clinical Oncology 38, № 15_suppl (2020): 6004. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.6004.

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6004 Background: Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. As part of the Phase 1b FORWARD II trial (NCT02606305), the combination of MIRV with bevacizumab (BEV) was evaluated in pts with FRα-positive (medium/high expression; ≥ 50%/ ≥75% of cells with PS2+ staining intensity), platinum agnostic ovarian cancer, defined as pts with either platinum resistant (PR) (recurrence within 6 months after last platinum dose) or platinum sensitive (PS) responded to the last platinum therapy rec

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Silver, Aliyah Brianne, and Jamie B. Spangler. "Design and characterization of a tumor-retained interleukin-2 cytokine/antibody fusion protein for cancer immunotherapy." Journal of Immunology 210, no. 1_Supplement (2023): 145.15. http://dx.doi.org/10.4049/jimmunol.210.supp.145.15.

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Abstract Interleukin-2 (IL-2) is a pleiotropic cytokine with clinical utility in stimulating anti-cancer immunity. However, its efficacy is limited by its short serum half-life, systemic toxicity, and concurrent activation of immunostimulatory and immunosuppressive immune cells. IL-2 can signal down an intermediate-affinity receptor consisting of IL-2 receptor β (IL-2Rβ) and the common gamma chain (γc) or a high-affinity receptor that also includes IL-2Rα. Regulatory T (Treg) cells express high levels of IL-2Rα making them more responsive to IL-2 than natural killer (NK), naïve/resting effecto

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Kumar, Anita, Toby A. Eyre, Katharine L. Lewis, Meghan C. Thompson, and Chan Y. Cheah. "New Directions for Mantle Cell Lymphoma in 2022." American Society of Clinical Oncology Educational Book, no. 42 (April 2022): 1–15. http://dx.doi.org/10.1200/edbk_349509.

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Mantle cell lymphoma is a rare B-cell non-Hodgkin lymphoma that is clinically and biologically heterogeneous. Risk stratification at the time of diagnosis is critical. One of the most powerful prognostic indices is the Mantle Cell Lymphoma International Prognostic Index-Combined, which integrates an estimate of proliferation (Ki67 index) with the standard Mantle Cell Lymphoma International Prognostic Index clinical factors. In addition, the presence of TP53 mutation is associated with suboptimal response to intensive chemoimmunotherapy and particularly dismal survival outcomes. Given their exc

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Chung, Chungwon J., Alfonso Clavijo, Mangkey A. Bounpheng, et al. "An improved, rapid competitive ELISA using a novel conserved 3B epitope for the detection of serum antibodies to foot-and-mouth disease virus." Journal of Veterinary Diagnostic Investigation 30, no. 5 (2018): 699–707. http://dx.doi.org/10.1177/1040638718779641.

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The highly contagious foot-and-mouth disease virus (FMDV) afflicts cloven-hoofed animals, resulting in significant costs because of loss of trade and recovery from disease. We developed a sensitive, specific, and rapid competitive ELISA (cELISA) to detect serum antibodies to FMDV. The cELISA utilized a monoclonal blocking antibody specific for a highly conserved FMDV nonstructural 3B epitope, a recombinant mutant FMDV 3ABC coating protein, and optimized format variables including serum incubation for 90 min at 20–25°C. Samples from 16 animals experimentally infected with one FMDV serotype (A,

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Angelopoulos, Panagiotis Agisilaos, Antonio Passaro, Ilaria Attili, et al. "Management of MET-Driven Resistance to Osimertinib in EGFR-Mutant Non-Small Cell Lung Cancer." Genes 16, no. 7 (2025): 772. https://doi.org/10.3390/genes16070772.

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Epidermal growth factor receptor (EGFR) mutations occur in approximately 10–20% of Caucasian and up to 50% of Asian patients with oncogene-addicted non-small cell lung cancer (NSCLC). Most frequently, alterations include exon 19 deletions and exon 21 L858R mutations, which confer sensitivity to EGFR tyrosine kinase inhibitors (TKIs). In the last decade, the third-generation EGFR-TKI osimertinib has represented the first-line standard of care for EGFR-mutant NSCLC. However, the development of acquired mechanisms of resistance significantly impacts long-term outcomes and represents a major thera

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Er, Jeremy, Rimes Joel, Light Amanda, Mark R. Dowling, Simon J. Harrison, and Edwin Hawkins. "Direct Visualisation of BCMA Bispecific Antibody and the Myeloma Immune Microenvironment." Blood 144, Supplement 1 (2024): 355. https://doi.org/10.1182/blood-2024-198851.

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Introduction: Multiple myeloma is haematological malignancy that remains difficult to cure despite recent therapeutic advances. Novel T cell redirecting therapies such as CAR-T cells and bispecific antibodies have shown promising efficacy in the relapse setting However, durable responses have yet to be achieved. Mechanisms of resistance and the dynamics of immune cell interactions within the bone marrow remain poorly defined. Here, we used in situ imaging of the bone marrow in living mice (intravital imaging) to characterise immune cell interactions with myeloma in the context of murine BCMA b

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Kannan, Nagarajan, Guruprasad Kalthur, Musheer Aalam, et al. "EGFR blockade leads to singular oncogene-addiction in ETV6-NTRK3 transformed human epithelial cells and hypersensitization to entrectinib." Journal of Clinical Oncology 39, no. 15_suppl (2021): e18055-e18055. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e18055.

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e18055 Background: Entrectinib, a TRK kinase inhibitor, has been approved for the treatment of tissue agnostic rare tumors positive for TRK fusions. A very low frequency molecular subset of TRK fusion tumors dubbed as secretory carcinoma (SC) are characterized by organ-agnostic epithelial origin, ETV6-NTRK3 (EN) fusion and distinguishable secretory-type tumor cells. These tumors have been frequently miscategorized as acinic cell carcinoma or adenocarcinoma. A previous mouse study identified EGF dependent epithelial progenitors as putative cell-of-origin for SC. Methods: To test the role of EGF

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Reiman, Derek, Godhev Kumar Manakkat Vijay, Heping Xu, et al. "Pseudocell Tracer—A method for inferring dynamic trajectories using scRNAseq and its application to B cells undergoing immunoglobulin class switch recombination." PLOS Computational Biology 17, no. 5 (2021): e1008094. http://dx.doi.org/10.1371/journal.pcbi.1008094.

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Single cell RNA sequencing (scRNAseq) can be used to infer a temporal ordering of cellular states. Current methods for the inference of cellular trajectories rely on unbiased dimensionality reduction techniques. However, such biologically agnostic ordering can prove difficult for modeling complex developmental or differentiation processes. The cellular heterogeneity of dynamic biological compartments can result in sparse sampling of key intermediate cell states. To overcome these limitations, we develop a supervised machine learning framework, called Pseudocell Tracer, which infers trajectorie

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Rogers, James V., Veronica L. Hall, and Charles C. McOsker. "Crumbling the Castle: Targeting DNABII Proteins for Collapsing Bacterial Biofilms as a Therapeutic Approach to Treat Disease and Combat Antimicrobial Resistance." Antibiotics 11, no. 1 (2022): 104. http://dx.doi.org/10.3390/antibiotics11010104.

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Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, increased misuse and overuse of existing antibiotics, and inadequate treatment options for biofilms formed during bacterial infections. Biofilms are complex microbiomes enshrouded in a self-produced extracellular polymeric substance (EPS) that is a primary defense mechanism of the resident microorganisms again

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Kraus, Fabian B. T., Elena Sultova, Kathrin Heinrich, et al. "Genetics and beyond: Precision Medicine Real-World Data for Patients with Cervical, Vaginal or Vulvar Cancer in a Tertiary Cancer Center." International Journal of Molecular Sciences 25, no. 4 (2024): 2345. http://dx.doi.org/10.3390/ijms25042345.

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Advances in molecular tumor diagnostics have transformed cancer care. However, it remains unclear whether precision oncology has the same impact and transformative nature across all malignancies. We conducted a retrospective analysis of patients with human papillomavirus (HPV)-related gynecologic malignancies who underwent comprehensive molecular profiling and subsequent discussion at the interdisciplinary Molecular Tumor Board (MTB) of the University Hospital, LMU Munich, between 11/2017 and 06/2022. We identified a total cohort of 31 patients diagnosed with cervical (CC), vaginal or vulvar c

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Singh, Kirit, Kelly Hotchkiss, Patrick Gedeon, et al. "IMMU-05. A PHASE I STUDY IN PROGRESS OF HEGFRVIII-CD3 BI-SCFV (BRITE) IN PATIENTS WITH WHO GRADE IV MALIGNANT GLIOMA." Neuro-Oncology Advances 3, Supplement_4 (2021): iv5. http://dx.doi.org/10.1093/noajnl/vdab112.018.

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Abstract INTRODUCTION Approximately 30% of glioblastomas harbor the tumor specific EGFRvIII mutation. hEGFRvIII-CD3 bi-scFv (Brain Bi-Specific T Cell Engager - BRiTE) is a novel bispecific antibody construct which can redirect a patient’s entire repertoire of T cells (TCR-agnostic) to specifically lyse EGFRvIII-positive tumor cells. Compared to CAR-T therapy, it offers a highly potent yet off-the-shelf approach for glioblastoma. BRiTE is now entering Phase I clinical trials (NCT04903795) and will be trialed as a monotherapy or with autologous T cell infusion. Migration of T cell binding macrom

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Shen, Shu Yi, Iulia Cirlan, Felicia Vincelli, et al. "Abstract 5024: Analytical performance of a genome-wide methylome enrichment platform to detect minimal residual disease from plasma-derived cell-free DNA." Cancer Research 84, no. 6_Supplement (2024): 5024. http://dx.doi.org/10.1158/1538-7445.am2024-5024.

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Abstract Introduction: Plasma-derived cell-free DNA (cfDNA) can be used to identify cancer signals, including minimal residual disease (MRD), in patients who have undergone curative cancer treatments. The cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) methodology is combined with custom algorithms that leverage differentially methylated regions (DMRs) found in cfDNA to distinguish between cancer and non-cancer signals. This novel non-degradative, tissue-agnostic approach was developed to bypass the limitations of bisulfite-sequencing and tissue-inform

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O'Malley, David M., Ana Oaknin, Ursula A. Matulonis та ін. "Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-agnostic ovarian cancer: Final analysis." Journal of Clinical Oncology 39, № 15_suppl (2021): 5504. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.5504.

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5504 Background: Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. As part of the Phase 1b FORWARD II trial (NCT02606305), the combination of MIRV with bevacizumab (BEV) was evaluated in pts with FRα-positive (medium/high expression; ≥50%/ ≥75% of cells with PS2+ staining intensity), platinum agnostic ovarian cancer, defined as pts with either platinum resistant (PROC) (recurrence within 6 months after last platinum dose) or platinum sensitive (PSOC)responded to the last platinum therapy a

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Kamaraju, Sailaja, Jonathan Thompson, Deepak Kilari, et al. "Abstract P2-10-24: ASTRO-VAC CNS : Bria-IMT in the Management of Tumor Agnostic Metastatic CNS Lesions." Clinical Cancer Research 31, no. 12_Supplement (2025): P2–10–24—P2–10–24. https://doi.org/10.1158/1557-3265.sabcs24-p2-10-24.

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Abstract Background: The Bria-IMT regimen has demonstrated the ability to induce a robust immune response and achieve disease control in heavily pre-treated advanced breast cancer (BC) patients. Bria-IMT is an irradiated allogeneic BC cell line that has been engineered to secrete GM-CSF and may function as antigen-presenting cells. Bria-IMT antigens are taken up by dendritic cells and presented to T cells, generating a tumor-directed immune response. Prior presentations report that Bria-IMT is able to induce regression of intracranial metastases. In the ongoing randomized phase 2 and (NCT03328

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Gu, Shenda, Irene Tang, Shirley Mihardja, et al. "Abstract 4245: QL301, a PD-L1 dependent 4-1BB agonist with enhanced preclinical anti-tumor efficacy and minimal liver toxicity." Cancer Research 82, no. 12_Supplement (2022): 4245. http://dx.doi.org/10.1158/1538-7445.am2022-4245.

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Abstract 4-1BB (CD137, TNFRSF9) is a potent co-stimulatory receptor found on T and NK cells. Activation of 4-1BB requires receptor clustering, which is naturally mediated by the endogenous trimeric 4-1BB ligand. Cross-linking via agnostic monoclonal antibodies can also activate 4-1BB but has generally resulted in unwanted side effects, mainly liver toxicity. To address the shortcomings of 4-1BB agonists, we have developed QL301, a PD-L1 x 4-1BB bispecific antibody that conditionally activates 4-1BB only when concurrently engaged to PD-L1, an immune checkpoint mediator elevated in the immuno-su

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Stalbovskaya, Viktoriya, Ernesto Wasserman, Jon Fryzek, Lauren C. Bylsma, and L. Andres Sirulnik. "NRG1 fusion-driven cancers: A systematic literature review and meta-analysis." Journal of Clinical Oncology 38, no. 15_suppl (2020): e15605-e15605. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e15605.

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e15605 Background: Neuregulin 1 (NRG1) fusion proteins have recently been identified as oncogenic drivers in diverse cancers with high unmet medical need. We recently reported promising responses in patients with cancers harboring NRG1 fusions treated with the bispecific antibody MCLA-128 (Schram 2019). The objective of this study was for the first time to quantitatively summarize the frequency of tumors harboring NRG1 fusions reported in the published literature. Methods: Neuregulin 1 (NRG1) fusion proteins have recently been identified as oncogenic drivers in diverse cancers with high unmet

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Au, Yu-Wah, Gemma Rigter, Wingyan Yu, et al. "Assessment of Ultra-Deep Mass Spectrometry Based Proteomics Compared to Flow Cytometry and RNA-Based Methods for the Discovery and Validation of Therapeutic Targets in Immune Cells." Blood 142, Supplement 1 (2023): 5377. http://dx.doi.org/10.1182/blood-2023-186623.

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Immuno-oncology (IO) has substantially improved the survival of cancer patients over the past several years encouraging the discovery of novel IO targets which are typically proteins expressed on the surface of immune cells. Sensitive quantification of proteins in complex biological samples is routinely achieved by immunoassays that use antibodies specific to target proteins. Such approaches can be a limitation in IO drug discovery since the development of de novo antibodies is associated with long lead times, high costs, and high failure rates, often resulting in the substitution of the prote

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Zhen, David B., Rachael A. Safyan, Eric Q. Konick, Ryan Nguyen, Colin C. Prichard, and E. Gabriela Chiorean. "The role of molecular testing in pancreatic cancer." Therapeutic Advances in Gastroenterology 16 (January 2023): 175628482311714. http://dx.doi.org/10.1177/17562848231171456.

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Pancreatic ductal adenocarcinoma (PDA) is highly aggressive and has few treatment options. To personalize therapy, it is critical to delineate molecular subtypes and understand inter- and intra-tumoral heterogeneity. Germline testing for hereditary genetic abnormalities is recommended for all patients with PDA and somatic molecular testing is recommended for all patients with locally advanced or metastatic disease. KRAS mutations are present in 90% of PDA, while 10% are KRAS wild type and are potentially targetable with epidermal growth factor receptor blockade. KRASG12C inhibitors have shown

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Sen, Shiraj, Mohamad Adham Salkeni, Costantine Albany, et al. "A multi-center, open-label phase 1/1b dose finding, safety, and pharmacokinetic study of MBRC-101, an Anth-EphA5 monomethyl auristatin (MMAE) antibody drug conjugate, in advanced refractory solid tumors." Journal of Clinical Oncology 42, no. 16_suppl (2024): TPS3161. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.tps3161.

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TPS3161 Background: EphA5 receptor is a member of the Ephrin receptor tyrosine kinase family. Several lines of compelling nonclinical evidence indicate EphA5 is a novel and selective target for solid tumor-directed therapy. Expressed only minimally in normal tissues, it is highly expressed in non-small cell lung carcinoma (NSCLC), head and neck squamous cell carcinoma (HNSCC), and breast, colorectal, pancreatic, gastric, and hepatic malignancies. MBRC-101 is a novel antibody drug conjugate (ADC) composed of an anti-EphA5 antibody conjugated to an MMAE payload (drug-to-antibody ratio of 4) thro

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Panovska, Dena, Asier Antoranz, Pieter-Jan Creemers, et al. "EXTH-20. SINGLE-CELL DRUG ACTIVITY MAPPING IN GLIOBLASTOMA IDENTIFIES EXTENDED DRUG RESPONSE HETEROGENEITY AND THERAPY-INDUCED CELLULAR PLASTICITY." Neuro-Oncology 23, Supplement_6 (2021): vi167. http://dx.doi.org/10.1093/neuonc/noab196.659.

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Abstract Glioblastoma (GBM) remains a highly malignant and incurable brain tumour. The inability to achieve clinical improvements in GBM treatment can be attributed to the excessive heterogeneity and plasticity of GBM cells, which is reflected by the presence of various cellular states within each tumour. How each of these tumour cell subtypes respond to therapy remains largely unknown. In this work, we developed a functional diagnostic analysis pipeline to measure therapeutic activity in GBM tumour cells at single-cell resolution using mass cytometry by time-of-flight (CyTOF). By applying an

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Keane, J. T., Oula K. Dagher, Fang Liu, and Avery D. Posey. "Abstract 58: Immunocytokines with specificity for invariant region of CAR molecules enhance effector function of multiple CAR T cell therapies." Cancer Research 84, no. 6_Supplement (2024): 58. http://dx.doi.org/10.1158/1538-7445.am2024-58.

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Abstract The effector functions of CAR T cells can be enhanced through delivery of immunostimulatory cytokines, such as IL-12, IL-18, or IL-23. However, systemic delivery of recombinant cytokines or paracrine secretion by CAR T cells can elicit toxicities due to non-specific targeting of the cytokines. Here, we designed immunocytokines with antibodies specific for the invariant linker peptides that join variable domains in the CAR scFv and immunostimulatory cytokines. The immunocytokines were capable of targeting CAR molecules agnostic of target antigen, demonstrating broad applicability witho

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Vanderlaag, Kathryn E., Anukriti Dhar, Arisa Paul, et al. "Abstract 338: Innovative strategy for enhancing the reach of HER3 antibody-drug conjugates: A novel drug combination approach." Cancer Research 85, no. 8_Supplement_1 (2025): 338. https://doi.org/10.1158/1538-7445.am2025-338.

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Abstract Antibody-drug conjugates (ADC) and radioligand therapies (RLT) have emerged as promising treatment modalities for various cancers. In recent years, there have been numerous approvals of ADCs and RLTs by regulatory agencies, highlighting their clinical success. Despite their success, they still suffer from a common challenge: tumor heterogeneity. Tumor heterogeneity limits not only the patient response, but also the eligible patient population for these therapies. To address this challenge, we have developed a high throughput screening platform to identify small molecule “priming” agen

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Gaudio, Mariangela, Michela Cinquini, Flavia Jacobs, et al. "Abstract P2-07-30: Exploring Treatment Options Following Progression to CDK4/6 Inhibitor in Hormone Receptor-Positive/HER2-Negative Advanced Breast Cancer: A Systematic Review and Network Meta-analysis." Clinical Cancer Research 31, no. 12_Supplement (2025): P2–07–30—P2–07–30. https://doi.org/10.1158/1557-3265.sabcs24-p2-07-30.

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Abstract Introduction: The treatment algorithm following progression on CDK4/6 inhibitors (CDK4/6i) remains uncertain. This study aimed to conduct a comprehensive systematic review and the first network meta-analysis to evaluate the efficacy and safety of new drugs (or combined new drugs) for the treatment of Hormone Receptor-Positive/HER2-Negative (HR+/HER2-) advanced breast cancer (ABC) in patients who have progressed after first-line treatment with CDK4/6i. Methods: PubMed, Embase, and Cochrane Central were searched from 2000 to 2024 and conference proceedings from major congresses of the l

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Medford, Arielle J., Lauren Oshry, Baris Boyraz, et al. "TRK inhibitor in a patient with metastatic triple-negative breast cancer and NTRK fusions identified via cell-free DNA analysis." Therapeutic Advances in Medical Oncology 15 (January 2023): 175883592311528. http://dx.doi.org/10.1177/17588359231152844.

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Tissue-agnostic indications for targeted therapies have expanded options for patients with advanced solid tumors. The Food and Drug Administration approvals of the programmed death-ligand 1 inhibitor pembrolizumab and the TRK inhibitors larotrectinib and entrectinib provide rationale for next-generation sequencing (NGS) in effectively all advanced solid tumor patients given potential for clinical responses even in otherwise refractory disease. As proof of concept, this case report describes a 64-year-old woman with triple-negative breast cancer refractory to multiple lines of therapy, found to

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Mackay, Helen, Anna Tinker, Brad Nelson, et al. "CRI-CCTG-0003/IND.240: An immunotherapy platform study in platinum-resistant high grade serous ovarian cancer (IPROC)." Journal of Clinical Oncology 41, no. 16_suppl (2023): TPS5617. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.tps5617.

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TPS5617 Background: Identifying new treatments for patients with platinum-resistant high grade serous ovarian cancer (HGSC) is a priority. Although several biological features of HGSC suggest inherent immunogenicity, immunotherapy has had limited efficacy to date. IPROC is an adaptive platform trial designed to evaluate multiple immunotherapy combinations selected and informed by an expert panel. IPROC accommodates both biomarker-agnostic and biomarker-directed combinations. Protocol and sub study specific translational studies are conducted on archived diagnostic tissue and serial prospective

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Cho, Doah, Sarah J. Lord, John Simes, et al. "Next-generation sequencing, should I use anti-HER2 therapy for HER2-amplified tumors off-label? Illustrating an extrapolation framework." Therapeutic Advances in Medical Oncology 14 (January 2022): 175883592211128. http://dx.doi.org/10.1177/17588359221112822.

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Background: Next-generation sequencing is used to increase targeted treatment opportunities, particularly for patients who have exhausted standard options. Where randomized controlled trial evidence for a targeted therapy is available for molecular alterations in one tumor type, the dilemma for the clinician is whether ‘matching’ targeted agents should be recommended off-label for the same molecular alterations detected in other tumor types, for which no trial data are available to guide practice. To judge the likely benefits, it may be possible to extrapolate evidence from cancers where treat

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"Tumor-Agnostic Treatment Heading to the Clinic?" Cancer Discovery, October 27, 2023, OF1. http://dx.doi.org/10.1158/2159-8290.cd-nd2023-0013.

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Abstract The antibody–drug conjugate trastuzumab deruxtecan could soon be the first therapy of its kind to be approved as a tumor-agnostic treatment for HER2-mutant or -expressing tumors. However, appropriate patient selection and adverse event management will be key to maximizing its benefit.

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Minott, Jessica A., Jacob P. van Vloten, Jacob G. E. Yates, et al. "Multiplex flow cytometry-based assay for quantifying tumor- and virus-associated antibodies induced by immunotherapies." Frontiers in Immunology 13 (November 16, 2022). http://dx.doi.org/10.3389/fimmu.2022.1038340.

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Novel immunotherapies continue to be developed and tested for application against a plethora of diseases. The clinical translation of immunotherapies requires an understanding of their mechanisms. The contributions of antibodies in driving long-term responses following immunotherapies continue to be revealed given their diverse effector functions. Developing an in-depth understanding of the role of antibodies in treatment efficacy is required to optimize immunotherapies and improve the chance of successfully translating them into the clinic. However, analyses of antibody responses can be chall

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"HER2-Targeted Therapy Shows Promise across Tumor Types." Cancer Discovery, June 6, 2023, OF1. http://dx.doi.org/10.1158/2159-8290.cd-nb2023-0047.

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Abstract The antibody–drug conjugate trastuzumab deruxtecan shows promising activity across multiple types of HER2-expressing advanced solid tumors, including traditionally hard-to-treat malignancies, according to data from the DESTINY-PanTumor02 trial. The ongoing study may pave the way for approval of a tumor-agnostic therapy for HER2-expressing and HER2-mutated cancers.

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