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Artykuły w czasopismach na temat „Antibody-toxin conjugates”

Autor: Grafiati

Data publikacji: 4 czerwca 2021

Data aktualizacji: 26 stycznia 2023

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1

Esteva, Francisco J., Kathy D. Miller, and Beverly A. Teicher. "What Can We Learn about Antibody-Drug Conjugates from the T-DM1 Experience?" American Society of Clinical Oncology Educational Book, no. 35 (May 2015): e117-e125. http://dx.doi.org/10.14694/edbook_am.2015.35.e117.

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Antibody conjugates are a diverse class of therapeutics that consist of a cytotoxic agent linked covalently to an antibody or antibody fragment directed toward a specific cell surface target expressed by tumor cells. The notion that antibodies directed toward targets on the surface of malignant cells could be used for drug delivery is not new. The history of antibody conjugates has been marked by hurdles identified and overcome. Early conjugates used mouse antibodies, drugs that either were not sufficiently potent, were immunogenic (proteins), or were too toxic, and linkers that were not suffi

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2

Ahmad, Ateeq, and Kevin Law. "Strategies for designing antibody-toxin conjugates." Trends in Biotechnology 6, no. 10 (October 1988): 246–51. http://dx.doi.org/10.1016/0167-7799(88)90056-x.

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Govindan, Serengulam V., and David M. Goldenberg. "New Antibody Conjugates in Cancer Therapy." Scientific World JOURNAL 10 (2010): 2070–89. http://dx.doi.org/10.1100/tsw.2010.191.

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Targeting of radiation, drugs, and protein toxins to cancers selectively with monoclonal antibodies (MAbs) has been a topic of considerable interest and an area of continued development. Radioimmunotherapy (RAIT) of lymphoma using directly labeled MAbs is of current interest after approval of two radiolabeled anti-CD20 MAbs, as illustrated with the near 100% overall response rate obtained in a recent clinical trial using an investigational radiolabeled anti-CD22 MAb,90Y-epratuzumab. The advantage of pretargeted RAIT over directly labeled MAbs is continuing to be validated in preclinical models

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4

Liang, X. P., M. E. Lamm, and J. G. Nedrud. "Oral administration of cholera toxin-Sendai virus conjugate potentiates gut and respiratory immunity against Sendai virus." Journal of Immunology 141, no. 5 (September 1, 1988): 1495–501. http://dx.doi.org/10.4049/jimmunol.141.5.1495.

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Abstract Successful oral immunization to prevent infectious diseases in the gastrointestinal tract as well as distant mucosal tissues may depend on the effectiveness of an Ag to induce gut immune responses. We and others have previously reported that cholera toxin possesses strong adjuvant effects on the gut immune response to co-administered Ag. To explore further adjuvant effects of cholera toxin, the holotoxin or its B subunit was chemically cross-linked to Sendai virus. The resulting conjugates, which were not infectious, were evaluated for their capacity to induce gut immune responses aga

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5

Panjideh, Hossein, Nicole Niesler, Alexander Weng, and Hendrik Fuchs. "Improved Therapy of B-Cell Non-Hodgkin Lymphoma by Obinutuzumab-Dianthin Conjugates in Combination with the Endosomal Escape Enhancer SO1861." Toxins 14, no. 7 (July 13, 2022): 478. http://dx.doi.org/10.3390/toxins14070478.

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Immunotoxins do not only bind to cancer-specific receptors to mediate the elimination of tumor cells through the innate immune system, but also increase target cytotoxicity by the intrinsic toxin activity. The plant glycoside SO1861 was previously reported to enhance the endolysosomal escape of antibody-toxin conjugates in non-hematopoietic cells, thus increasing their cytotoxicity manifold. Here we tested this technology for the first time in a lymphoma in vivo model. First, the therapeutic CD20 antibody obinutuzumab was chemically conjugated to the ribosome-inactivating protein dianthin. The

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6

Faria, Morse, Marlking Peay, Brandon Lam, Eric Ma, Moucun Yuan, Michael Waldron, William Mylott, Meina Liang, and Anton Rosenbaum. "Multiplex LC-MS/MS Assays for Clinical Bioanalysis of MEDI4276, an Antibody-Drug Conjugate of Tubulysin Analogue Attached via Cleavable Linker to a Biparatopic Humanized Antibody against HER-2." Antibodies 8, no. 1 (January 11, 2019): 11. http://dx.doi.org/10.3390/antib8010011.

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Bioanalysis of complex biotherapeutics, such as antibody-drug conjugates (ADCs), is challenging and requires multiple assays to describe their pharmacokinetic (PK) profiles. To enable exposure-safety and exposure-efficacy analyses, as well as to understand the metabolism of ADC therapeutics, three bioanalytical methods are typically employed: Total Antibody, Antibody Conjugated Toxin or Total ADC and Unconjugated Toxin. MEDI4276 is an ADC comprised of biparatopic humanized antibody attached via a protease-cleavable peptide-based maleimidocaproyl linker to a tubulysin toxin (AZ13599185) with an

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7

Yu, Rui, Junjie Xu, Tao Hu, and Wei Chen. "The Pneumococcal Polysaccharide-Tetanus Toxin Native C-Fragment Conjugate Vaccine: The Carrier Effect and Immunogenicity." Mediators of Inflammation 2020 (July 4, 2020): 1–11. http://dx.doi.org/10.1155/2020/9596129.

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The encapsulated bacteria, as Streptococcus pneumonia, Haemophilus influenzae type b, and Neisseria meningitidis, cause serious morbidity and mortality worldwide. The capsular polysaccharide (PS), which could elicit a weak T cell-independent immune response, is a vital virulence determinant. One of the strategies to improve the PS-specific immunogenicity is to conjugate PS with a nontoxic carrier protein. Tetanus toxoid (TT) and CRM197 are the typical carrier proteins for the PS conjugate vaccines. TT is the inactivated tetanus toxin manipulated with formaldehyde, which suffers from the pollut

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8

Marsh, J. W., and D. M. Neville. "A flexible peptide spacer increases the efficacy of holoricin anti-T cell immunotoxins." Journal of Immunology 140, no. 10 (May 15, 1988): 3674–78. http://dx.doi.org/10.4049/jimmunol.140.10.3674.

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Abstract Immunotoxins, constructed by chemically cross-linking an antibody and protein toxin, do not possess the high efficacy of the native toxin. Decreases in toxicity are due in part to the steric constraints imposed on the two macromolecules, which result in both decreased antibody binding and toxin function. In examining the structural features that influence efficacy in holotoxin-antibody conjugates, it was found that the incorporation of a 29-residue polypeptide, derived from the insulin B chain between the antibody and ricin moiety, resulted in an increase in both potency and efficacy.

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9

Govindan, Serengulam V., Gary L. Griffiths, Hans J. Hansen, Ivan D. Horak, and David M. Goldenberg. "Cancer Therapy with Radiolabeled and Drug/Toxin-conjugated Antibodies." Technology in Cancer Research & Treatment 4, no. 4 (August 2005): 375–91. http://dx.doi.org/10.1177/153303460500400406.

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Radioimmunotherapy and antibody-directed chemotherapy have emerged as cancer treatment modalities with the regulatory approval of products for non-Hodgkin's lymphoma and acute myeloid leukemia. Antibody-toxin therapy is likewise on the verge of clinical fruition. Accumulating evidence suggests that radioimmunotherapy may have the best impact in minimal-disease and adjuvant settings, especially with radioresistant solid tumors. For the latter, ongoing efforts in ‘pretargeting’ to increase deliverable tumor radiation dose, combination therapies, and locoregional applications are also of importan

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10

Lefeber, Dirk J., Barry Benaissa-Trouw, Johannes F. G. Vliegenthart, Johannis P. Kamerling, Wouter T. M. Jansen, Kees Kraaijeveld, and Harm Snippe. "Th1-Directing Adjuvants Increase the Immunogenicity of Oligosaccharide-Protein Conjugate Vaccines Related to Streptococcus pneumoniae Type 3." Infection and Immunity 71, no. 12 (December 2003): 6915–20. http://dx.doi.org/10.1128/iai.71.12.6915-6920.2003.

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ABSTRACT Oligosaccharide (OS)-protein conjugates are promising candidate vaccinesagainst encapsulated bacteria, such as Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae. Although the effects of several variables such as OS chain length and protein carrier have been studied, little is known about the influence of adjuvants on the immunogenicity of OS-protein conjugates. In this study, a minimal protective trisaccharide epitope of Streptococcus pneumoniae type 3 conjugated to the cross-reacting material of diphtheria toxin was used for immunization of BALB/c mice in t

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11

Messerschmidt, Katrin, and Katja Heilmann. "Toxin–antigen conjugates as selection tools for antibody producing cells." Journal of Immunological Methods 387, no. 1-2 (January 2013): 167–72. http://dx.doi.org/10.1016/j.jim.2012.10.010.

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ARNDT, R., and H. J. THIESEN. "Elimination of Trinitrophenol-Specific Antibody Response by Antigen-Toxin Conjugates." Scandinavian Journal of Immunology 22, no. 5 (November 1985): 489–94. http://dx.doi.org/10.1111/j.1365-3083.1985.tb01907.x.

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13

Ou, Li, Krishana Gulla, Andrea Biju, Daniel W. Biner, Tatsiana Bylund, Anita Changela, Steven J. Chen, et al. "Assessment of Crosslinkers between Peptide Antigen and Carrier Protein for Fusion Peptide-Directed Vaccines against HIV-1." Vaccines 10, no. 11 (November 12, 2022): 1916. http://dx.doi.org/10.3390/vaccines10111916.

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Conjugate-vaccine immunogens require three components: a carrier protein, an antigen, and a crosslinker, capable of coupling antigen to carrier protein, while preserving both T-cell responses from carrier protein and B-cell responses from antigen. We previously showed that the N-terminal eight residues of the HIV-1 fusion peptide (FP8) as an antigen could prime for broad cross-clade neutralizing responses, that recombinant heavy chain of tetanus toxin (rTTHC) as a carrier protein provided optimal responses, and that choice of crosslinker could impact both antigenicity and immunogenicity. Here,

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14

Johansson, Eva-Liz, Carola Rask, Margareta Fredriksson, Kristina Eriksson, Cecil Czerkinsky, and Jan Holmgren. "Antibodies and Antibody-Secreting Cells in the Female Genital Tract after Vaginal or Intranasal Immunization with Cholera Toxin B Subunit or Conjugates." Infection and Immunity 66, no. 2 (February 1, 1998): 514–20. http://dx.doi.org/10.1128/iai.66.2.514-520.1998.

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ABSTRACT We studied the antibody response including antibody-secreting cells (ASC) in the female genital tract of mice after mucosal immunizations with the recombinant B subunit of cholera toxin (rCTB) perorally, intraperitoneally, vaginally, and intranasally (i.n.). The strongest genital antibody responses as measured with a novel perfusion-extraction method were induced after vaginal and i.n. immunizations, and these routes also gave rise to specific immunoglobulin A (IgA) and IgG ASC in the genital mucosa. Specific ASC in the iliac lymph nodes, which drain the female genital tract, were see

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15

Chen, Zhaochun, Rachel Schneerson, Julie A. Lovchik, Zhongdong Dai, Joanna Kubler-Kielb, Liane Agulto, Stephen H. Leppla, and Robert H. Purcell. "Bacillus anthracis Capsular Conjugates Elicit Chimpanzee Polyclonal Antibodies That Protect Mice from Pulmonary Anthrax." Clinical and Vaccine Immunology 22, no. 8 (June 3, 2015): 902–8. http://dx.doi.org/10.1128/cvi.00137-15.

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ABSTRACTThe immunogenicity ofBacillus anthraciscapsule (poly-γ-d-glutamic acid [PGA]) conjugated to recombinantB. anthracisprotective antigen (rPA) or to tetanus toxoid (TT) was evaluated in two anthrax-naive juvenile chimpanzees. In a previous study of these conjugates, highly protective monoclonal antibodies (MAbs) against PGA were generated. This study examines the polyclonal antibody response of the same animals. Preimmune antibodies to PGA with titers of >103were detected in the chimpanzees. The maximal titer of anti-PGA was induced within 1 to 2 weeks following the 1st immunization, w

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16

Trad, Ahmad, Hinrich P. Hansen, Mohammad Shomali, Matthias Peipp, Katja Klausz, Nina Hedemann, Kosuke Yamamoto, et al. "ADAM17-overexpressing breast cancer cells selectively targeted by antibody–toxin conjugates." Cancer Immunology, Immunotherapy 62, no. 3 (September 1, 2012): 411–21. http://dx.doi.org/10.1007/s00262-012-1346-x.

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Bergquist, C., T. Lagergård, M. Lindblad, and J. Holmgren. "Local and systemic antibody responses to dextran-cholera toxin B subunit conjugates." Infection and immunity 63, no. 5 (1995): 2021–25. http://dx.doi.org/10.1128/iai.63.5.2021-2025.1995.

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Sellrie, F., and B. Micheel. "Selection of recombinant antibody-producing E. coli cells by means of toxin conjugates." Biochemical Engineering Journal 38, no. 3 (March 2008): 309–13. http://dx.doi.org/10.1016/j.bej.2007.07.017.

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Tedder, T. F., V. S. Goldmacher, J. M. Lambert, and S. F. Schlossman. "Epstein Barr virus binding induces internalization of the C3d receptor: a novel immunotoxin delivery system." Journal of Immunology 137, no. 4 (August 15, 1986): 1387–91. http://dx.doi.org/10.4049/jimmunol.137.4.1387.

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Abstract Epstein Barr virus (EBV) infection of human B lymphocytes is initiated by selective binding of the virus to the C3d receptor (EBV/C3d receptor) on the cell surface and results in polyclonal proliferation of infected cells. In these studies we examined the fate of the EBV/C3d receptor during viral infection by using an immunotoxin made from a monoclonal antibody (HB5) reactive with the receptor and the potent toxin, gelonin. Binding of the HB5-gelonin conjugate to the EBV/C3d receptor before EBV infection (at concentrations as low as 10(-11) M) significantly inhibited the subsequent po

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20

Price, Gregory A., Michael W. Russell, and Cynthia Nau Cornelissen. "Intranasal Administration of Recombinant Neisseria gonorrhoeae Transferrin Binding Proteins A and B Conjugated to the Cholera Toxin B Subunit Induces Systemic and Vaginal Antibodies in Mice." Infection and Immunity 73, no. 7 (July 2005): 3945–53. http://dx.doi.org/10.1128/iai.73.7.3945-3953.2005.

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ABSTRACT The transferrin binding proteins (TbpA and TbpB) comprise the gonococcal transferrin receptor and are considered potential antigens for inclusion in a vaccine against Neisseria gonorrhoeae. Intranasal (IN) immunization has shown promise in development of immunity against sexually transmitted disease pathogens, in part due to the induction of antigen-specific genital tract immunoglobulin A (IgA) and IgG. Conjugation of antigens to the highly immunogenic cholera toxin B subunit (Ctb) enhances antibody responses in the serum and mucosal secretions following IN vaccination. In the current

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Speirs, Joan I., and Mumtaz Akhtar. "Detection of Escherichia coli cytotoxins by enzyme-linked immunosorbent assays." Canadian Journal of Microbiology 37, no. 8 (August 1, 1991): 650–53. http://dx.doi.org/10.1139/m91-110.

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Sandwich enzyme-linked immunosorbent assays (ELISAs) were developed to detect Escherichia coli cytotoxins. Wells were coated with monoclonal antibodies from hybridomas 13C4 and (or) 11E10, and biotin conjugates of these antibodies were used for detecting verotoxin 1 and Shiga-like toxin II, respectively. Sensitivities were about 100 and 200 cytotoxic doses, respectively. Verotoxin 2 was detected by ELISA with monoclonal antibody 11E10, but at a sensitivity of only about 4000 cytotoxic doses. ELISA results of polymyxin-treated cell extracts from cultures of 67 E. coli strains were in agreement

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Seong, Seung-Yong, Nam-Hyuk Cho, Ick Chan Kwon, and Seo Young Jeong. "Protective Immunity of Microsphere-Based Mucosal Vaccines against Lethal Intranasal Challenge withStreptococcus pneumoniae." Infection and Immunity 67, no. 7 (July 1, 1999): 3587–92. http://dx.doi.org/10.1128/iai.67.7.3587-3592.1999.

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ABSTRACT Mucosal vaccination of capsular polysaccharide (PS) ofStreptococcus pneumoniae and subsequent creation of the first line of immunological defense in mucosa were examined. Mucosal as well as systemic antibody responses to PS were evoked by peroral or intranasal immunization of BALB/c mice with PS-cholera toxin B subunit (CTB) conjugates entrapped in the alginate microspheres (AM). The bacterial colonization at the lung mucosa was most profoundly inhibited (<95%) by intranasal immunization with the naked conjugate (PS-CTB). The mice vaccinated orally with encapsulated conjugate [AM(P

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23

Polito, Letizia, Giulia Calafato, Massimo Bortolotti, Cecilia Chiarelli Olivari, Stefania Maiello, and Andrea Bolognesi. "Antibody Conjugates for Sarcoma Therapy: How Far along Are We?" Biomedicines 9, no. 8 (August 8, 2021): 978. http://dx.doi.org/10.3390/biomedicines9080978.

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Sarcomas are one of the most difficult type of cancer to manage and treat because of their extremely heterogeneous molecular and morphological features. Despite the progress made over the years in the establishment of standard protocols for high and low grading/staging sarcoma patients, mostly with chemotherapy and/or radiotherapy, 50% of treated patients experience relapse episodes. Because of this, in the last 20 years, new therapeutic approaches for sarcoma treatment have been evaluated in preclinical and clinical studies. Among them, antibody-based therapies have been the most studied. Imm

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Karsten, Lennard, Nils Janson, Vadim Le Joncour, Sarfaraz Alam, Benjamin Müller, Jayendrakishore Tanjore Ramanathan, Pirjo Laakkonen, Norbert Sewald, and Kristian M. Müller. "Bivalent EGFR-Targeting DARPin-MMAE Conjugates." International Journal of Molecular Sciences 23, no. 5 (February 23, 2022): 2468. http://dx.doi.org/10.3390/ijms23052468.

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Epidermal growth factor receptor (EGFR) is a validated tumor marker overexpressed in various cancers such as squamous cell carcinoma (SSC) of the head and neck and gliomas. We constructed protein-drug conjugates based on the anti-EGFR Designed Ankyrin Repeat Protein (DARPin) E01, and compared the bivalent DARPin dimer (DD1) and a DARPin-Fc (DFc) to the monomeric DARPin (DM) and the antibody derived scFv425-Fc (scFvFc) in cell culture and a mouse model. The modular conjugation system, which was successfully applied for the preparation of protein-drug and -dye conjugates, uses bio-orthogonal pro

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Peeters, C. C., A. M. Tenbergen-Meekes, C. J. Heijnen, J. T. Poolman, B. J. Zegers, and G. T. Rijkers. "In vitro induction of a Haemophilus influenzae type b polysaccharide-specific antibody response in human peripheral blood lymphocytes of individuals recently vaccinated with an oligosaccharide-protein conjugate." Journal of Immunology 147, no. 12 (December 15, 1991): 4192–99. http://dx.doi.org/10.4049/jimmunol.147.12.4192.

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Abstract In this paper an in vitro culture system for the induction of an antibody response to the Haemophilus influenzae type b polysaccharide (PRP) is described. Anti-PRP IgM and IgG antibody-secreting cells (ASC) and anti-diphtheria toxoid (DT) IgG ASC were detected in cultures of blood B and T cells derived from donors 4 to 6 wk after immunization with Haemophilus influenzae type b oligosaccharide-mutant diphtheria toxin (CRM197) conjugate (HbOC) and required in vitro restimulation with HbOC. When lymphocytes from HbOC-vaccinated donors were stimulated with PRP, anti-PRP IgM and IgG ASC co

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Lu, Ying-Jie, Sophie Forte, Claudette M. Thompson, Porter W. Anderson, and Richard Malley. "Protection against Pneumococcal Colonization and Fatal Pneumonia by a Trivalent Conjugate of a Fusion Protein with the Cell Wall Polysaccharide." Infection and Immunity 77, no. 5 (March 2, 2009): 2076–83. http://dx.doi.org/10.1128/iai.01554-08.

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ABSTRACT Cell wall polysaccharide (CWPS), pneumolysin, and surface adhesin A (PsaA) are antigens common to virtually all serotypes of Streptococcus pneumoniae (pneumococcus), and all have been studied separately for use in protection. Previously we showed that protection against nasopharyngeal (NP) colonization by intranasal vaccination of mice with killed pneumococci is mediated by TH17 cells and correlates with interleukin-17A (IL-17A) expression by T cells in vitro; we have also shown that CWPS and other species-common antigens protect against colonization by a similar mechanism. Here we ma

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Senter, Peter D., Marilyn J. Tansey, John M. Lambert, and Walter A. Blattler. "NOVEL PHOTOCLEAVABLE PROTEIN CROSSLINKING REAGENTS AND THEIR USE IN THE PREPARATION OF ANTIBODY-TOXIN CONJUGATES." Photochemistry and Photobiology 42, no. 3 (September 1985): 231–37. http://dx.doi.org/10.1111/j.1751-1097.1985.tb08936.x.

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Liu, Yongheng, Wei Lian, Xi Zhao, Wei Qi, Jian Xu, Liang Xiao, Yan Qing, Tongtong Xue, and Jingyi Wang. "A phase I study of safety and pharmacokinetics of A166, a novel selective inhibitor of human epidermal growth factor receptor-2 in Chinese patients with advanced solid tumors." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e13007-e13007. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e13007.

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e13007 Background: Human epidermal growth factor receptor 2 (HER2) is an effective therapeutic target for breast and gastric cancer. A166 is an antibody-drug conjugate composed of a novel cytotoxic drug (monomethyl auristatin F derivative ) site-specifically conjugated to transtuzumab sequence via a stable protease-cleavable valine citrulline linker, which has a DAR (Drug Antibody Ratio) of Better efficacy were observed in preclinical CDX and PDX studies including HER2 low expression and T-DM1 resistant models while toxicity studies demonstrated a good safety profile in cynomolgus monkey. Meth

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Dardevet, Lucie, Feten Najlaoui, Sonia Aroui, Mayeul Collot, Céline Tisseyre, Michael W. Pennington, Jean-Maurice Mallet, and Michel De Waard. "A Conjugate between Lqh-8/6, a Natural Peptide Analogue of Chlorotoxin, and Doxorubicin Efficiently Induces Glioma Cell Death." Biomedicines 10, no. 10 (October 17, 2022): 2605. http://dx.doi.org/10.3390/biomedicines10102605.

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Natural peptides isolated from animal venoms generally target cell surface receptors with high affinity and selectivity. On many occasions, some of these receptors are over-expressed in cancer cells. Herein, we identified Lqh-8/6 as a natural peptide analog of chlorotoxin, a proven and useful compound for the diagnosis and treatment of glioma. Lqh-8/6 and two other natural analogues were chemically synthesized for the first time and evaluated for their ability to label, detect and prevent glioma growth in vitro. We demonstrate that a biotinylated version of Lqh-8/6 allows both the labeling of

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Palanca-Wessels, Maria Corinna, and Oliver W. Press. "Advances in the treatment of hematologic malignancies using immunoconjugates." Blood 123, no. 15 (April 10, 2014): 2293–301. http://dx.doi.org/10.1182/blood-2013-10-492223.

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Abstract Monoclonal antibody therapy has revolutionized cancer treatment by significantly improving patient survival both in solid tumors and hematologic malignancies. Recent technological advances have increased the effectiveness of immunotherapy leading to its broader application in diverse treatment settings. Immunoconjugates (ICs) consist of a cytotoxic effector covalently linked to a monoclonal antibody that enables the targeted delivery of its therapeutic payload to tumors based on cell-surface receptor recognition. ICs are classified into 3 groups based on their effector type: immunotox

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Hammond, Philip W., Omid Vafa, Jonathan Jacinto, Jost Vielmetter, Sher Karki, Sean Yoder, Greg Lazar, et al. "A Humanized Anti-CD30 Monoclonal Antibody, XmAb™2513, with Enhanced In Vitro Potency Against CD30-Positive Lymphomas Mediated by High Affinity Fc-Receptor Binding." Blood 106, no. 11 (November 16, 2005): 1470. http://dx.doi.org/10.1182/blood.v106.11.1470.1470.

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Abstract CD30 (also known as Ki-1), a member of the TNF-receptor superfamily, is normally expressed at low levels on activated lymphocytes and has been implicated in cell death and T-cell proliferation. CD30 is highly expressed in Hodgkin’s disease, (HD) and in Anaplastic Large Cell Lymphoma (ALCL). Unmodified CD30 antibodies as well as anti-CD30 based bi-specific antibodies, antibody-toxin conjugates, and radioimmuno-therapeutics have examined CD30 as a therapeutic target in preclinical and clinical studies. Unmodified antibodies have met with limited success and a lack of engagement of immun

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Porath, Kendra A., Ann Mladek, Rachael A. Vaubel, Michael S. Regan, Sonia Jain, Danielle Burgenske, Katrina Bakken, et al. "Abstract 334: Convection enhanced delivery of EGFR-targeting antibody drug conjugates ABBV-321 and Depatux-M." Cancer Research 82, no. 12_Supplement (June 15, 2022): 334. http://dx.doi.org/10.1158/1538-7445.am2022-334.

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Abstract Introduction: EGFR targeted antibody-drug conjugates (ADCs) show promise as a novel treatment in a subset of glioblastoma (GBM). Two EGFR targeting ADCs include first generation Depatux-M, with an antimitotic toxin monomethyl auristatin F (MMAF), and ABBV-321, with a DNA crosslinking agent pyrrolobenzodiazepine dimer (PBD) toxin. Due to the large molecular weight, poor drug distribution across the blood-brain barrier significantly limits the efficacy in EGFR-amplified GBM. We studied whether convection enhanced delivery (CED) can be used to safely infuse these two EGFR-targeted ADCs i

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Ambrosino, D. M., D. Bolon, H. Collard, R. Van Etten, M. V. Kanchana, and R. W. Finberg. "Effect of Haemophilus influenzae polysaccharide outer membrane protein complex conjugate vaccine on macrophages." Journal of Immunology 149, no. 12 (December 15, 1992): 3978–83. http://dx.doi.org/10.4049/jimmunol.149.12.3978.

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Abstract Haemophilus influenzae type b polysaccharide-conjugate vaccines elicit protective antibody responses in young infants. One of these conjugates, polysaccharide linked to outer membrane protein complex (PRP-OMPC), is produced by linking the capsular polysaccharide to an outer membrane protein complex derived from group B Neisseria meningitidis. The outer membrane protein complex contains T cell carrier epitopes that elicit T cell-dependent antibody responses. OMPC also has been shown to increase the antibody response to other proteins administered concurrently that are not covalently li

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Delprino, Laura, Maria Giacomotti, Franco Dosio, Paola Brusa, Maurizio Ceruti, Giorgio Grosa, and Luigi Cattel. "Toxin-Targeted Design for Anticancer Therapy. II: Preparation and Biological Comparison of Different Chemically Linked Gelonin-Antibody Conjugates." Journal of Pharmaceutical Sciences 82, no. 7 (July 1993): 699–704. http://dx.doi.org/10.1002/jps.2600820706.

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Hamamichi, Shusei, Takeshi Fukuhara, and Nobutaka Hattori. "Immunotoxin Screening System: A Rapid and Direct Approach to Obtain Functional Antibodies with Internalization Capacities." Toxins 12, no. 10 (October 15, 2020): 658. http://dx.doi.org/10.3390/toxins12100658.

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Toxins, while harmful and potentially lethal, have been engineered to develop potent therapeutics including cytotoxins and immunotoxins (ITs), which are modalities with highly selective targeting capabilities. Currently, three cytotoxins and IT are FDA-approved for treatment of multiple forms of hematological cancer, and additional ITs are tested in the clinical trials or at the preclinical level. For next generation of ITs, as well as antibody-mediated drug delivery systems, specific targeting by monoclonal antibodies is critical to enhance efficacies and reduce side effects, and this methodo

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Riedl, Thilo, Egon van Boxtel, Martijn Bosch, Paul W. H. I. Parren, and Arnout F. Gerritsen. "High-Throughput Screening for Internalizing Antibodies by Homogeneous Fluorescence Imaging of a pH-Activated Probe." Journal of Biomolecular Screening 21, no. 1 (October 30, 2015): 12–23. http://dx.doi.org/10.1177/1087057115613270.

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Antibody-drug conjugates (ADCs) represent a rapidly growing class of biotherapeutics that deliver drugs specifically to target cells by binding of the antibody component to surface receptors. The majority of ADCs require receptor internalization depending on intrinsic features of the specific ADC-antigen interaction. The development of potent ADCs would greatly benefit from the identification of efficiently internalizing antibodies at early stages of discovery. We developed a highly sensitive and rapid antibody internalization assay using an indirect Cypher5E label. The pH-activated CypHer5E l

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Passwell, Justen H., Efrat Harlev, Shai Ashkenazi, Chiayung Chu, Dan Miron, Reut Ramon, Naheed Farzan, et al. "Safety and Immunogenicity of ImprovedShigella O-Specific Polysaccharide-Protein Conjugate Vaccines in Adults in Israel." Infection and Immunity 69, no. 3 (March 1, 2001): 1351–57. http://dx.doi.org/10.1128/iai.69.3.1351-1357.2001.

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ABSTRACT Data suggest that the O-specific polysaccharide (O-SP) domain of the lipopolysaccharide (LPS) of Shigella species is both an essential virulence factor and a protective antigen and that a critical level of serum immunoglobulin G (IgG) to this antigen will confer immunity to shigellosis. Because covalent attachment of polysaccharides to proteins increases their immunogenicity, especially in infants and in young children, the O-SP of Shigella species were bound to medically useful proteins, and the safety and immunogenicity of the resultant conjugates were confirmed in adults and 4- to

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Pestka, James J. "Enhanced Surveillance of Foodborne Mycotoxins by Immunochemical Assay." Journal of AOAC INTERNATIONAL 71, no. 6 (November 1, 1988): 1075–81. http://dx.doi.org/10.1093/jaoac/71.6.1075.

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Abstract Mycotoxins are a chemically diverse group of fungal secondary metabolites with a wide range of toxic effects. Conventional thin-layer and instrumental methods of mycotoxin analysis are time-consuming and make routine safety and quality control screening of these compounds in agricultural commodities difficult. As an alternative, specific polyclonal and monoclonal antibodies have been raised against mycotoxin-protein conjugates and used in sensitive radioimmunoassays (RIAs) and enzyme-linked immunosorbent assays (ELISAs). One of the simplest ELISA approaches involves competition for a

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Niculescu-Duvaz, I., and C. J. Springer. "Antibody-Directed Enzyme Prodrug Therapy (ADEPT): A Targeting Strategy in Cancer Chemotherapy." Current Medicinal Chemistry 2, no. 3 (October 1995): 687–706. http://dx.doi.org/10.2174/092986730203220223143057.

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<P>Antibody-Directed Enzyme Prodrug Therapy (ADEPT) is a new conceptual approach designed to improve the selectivity of anti-cancer drugs. ADEPT separates the cytotoxic from the targeting function of immunoconjugates in a two phase system that has benefits over one phase chemo-, toxin- or radio-immunoconjugates. <P> This review, while discussing the basic prinicples of ADEPT and the main requirements for all the components (enzymes, prodrugs and antibodies) of the systems, also summarizes the latest results obtained with this technolo gy. The main components of ADEPT are described

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Laske, Douglas W., Orhan Ilercil, Aytac Akbasak, Richard J. Youle, and Edward H. Oldfield. "Efficacy of direct intratumoral therapy with targeted protein toxins for solid human gliomas in nude mice." Journal of Neurosurgery 80, no. 3 (March 1994): 520–26. http://dx.doi.org/10.3171/jns.1994.80.3.0520.

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✓ Targeted protein toxins are a new class of reagents with the potential for great tumor selectivity and cytotoxic potency. Two such compounds were studied: 1) Tf-CRM107, a conjugate of human transferrin (Tf) and diphtheria toxin with a point mutation (CRM107); and 2) 454A12-rRA, a conjugate of a monoclonal antibody (454A12) to the human Tf receptor and recombinant ricin A chain (rRA). Both compounds are potent and specific in killing human glioblastoma cell lines in vitro. The authors investigated the activity of these reagents administered intratumorally against solid U251 MG human gliomas i

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Shi, Xiarong, Leiliane P. Sousa, Elizabeth M. Mandel-Bausch, Francisco Tome, Andrey V. Reshetnyak, Yaron Hadari, Joseph Schlessinger, and Irit Lax. "Distinct cellular properties of oncogenic KIT receptor tyrosine kinase mutants enable alternative courses of cancer cell inhibition." Proceedings of the National Academy of Sciences 113, no. 33 (August 1, 2016): E4784—E4793. http://dx.doi.org/10.1073/pnas.1610179113.

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Large genomic sequencing analysis as part of precision medicine efforts revealed numerous activating mutations in receptor tyrosine kinases, including KIT. Unfortunately, a single approach is not effective for inhibiting cancer cells or treating cancers driven by all known oncogenic KIT mutants. Here, we show that each of the six major KIT oncogenic mutants exhibits different enzymatic, cellular, and dynamic properties and responds distinctly to different KIT inhibitors. One class of KIT mutants responded well to anti-KIT antibody treatment alone or in combination with a low dose of tyrosine k

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Maniecki, Maciej Bogdan, Henrik Hasle, Knud Bendix, and Holger Jon Møller. "Hepatotoxicity in Patients Treated with Gemtuzumab Ozogamicin - Specific Targeting of Hepatocytes?" Blood 114, no. 22 (November 20, 2009): 4150. http://dx.doi.org/10.1182/blood.v114.22.4150.4150.

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Abstract Abstract 4150 The immunotoxin gemtuzumab ozogamicin (Mylotarg‘, GO) comprises a potent cytotoxic agent, calicheamicin, and a recombinant humanized monoclonal antibody directed against CD33. GO is increasingly used for treatment of acute myeloid leukemia (AML) as CD33, a trans-membranous glycoprotein, is highly expressed on most leukemic blast cells, but, in normal cells confined to early multilineage hematopoietic progenitors and myelomonocytic precursors. Adverse effects of GO treatment are primarily related to myelosuppression (infections, fever, bleedings). However, severe sinusoid

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Valent, Peter, Irina Sadovnik, Gregor Eisenwort, Karin Bauer, Harald Herrmann, Karoline V. Gleixner, Axel Schulenburg, Werner Rabitsch, Wolfgang R. Sperr, and Dominik Wolf. "Immunotherapy-Based Targeting and Elimination of Leukemic Stem Cells in AML and CML." International Journal of Molecular Sciences 20, no. 17 (August 29, 2019): 4233. http://dx.doi.org/10.3390/ijms20174233.

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The concept of leukemic stem cells (LSC) has been developed with the idea to explain the clonal hierarchies and architectures in leukemia, and the more or less curative anti-neoplastic effects of various targeted drugs. It is now widely accepted that curative therapies must have the potential to eliminate or completely suppress LSC, as only these cells can restore and propagate the malignancy for unlimited time periods. Since LSC represent a minor cell fraction in the leukemic clone, little is known about their properties and target expression profiles. Over the past few years, several cell-sp

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Bendell, Johanna C., Judy Sing-Zan Wang, Babar Bashir, Debra L. Richardson, Gavin Bennett, Carly Campbell, Meliessa G. Hennessy, et al. "BT5528-100 phase I/II study of the safety, pharmacokinetics, and preliminary clinical activity of BT5528 in patients with advanced malignancies associated with EphA2 expression." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): TPS3655. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.tps3655.

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TPS3655 Background: BT5528 is a Bicycle Toxin Conjugate (BTC), comprising a bicyclic peptide targeting the tumor antigen EphA2, linked to a cytotoxin (monomethyl auristatin E [MMAE]) via a tumor microenvironment cleavable linker. Bicycles are a novel class of chemically synthesized constrained peptides, developed by Bicycle Therapeutics. EphA2 is reported to be overexpressed in a range of solid tumors, contributes to oncogenesis, tumor-associated angiogenesis and metastasis. Intracellular EphA2 signaling converges on pathways that are integral to cell growth, proliferation, migration and invas

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Cabello-Alemán, Lucía. "Future directions in cancer immunotherapy with monoclonal antibodies." Research Results in Pharmacology 8, no. 4 (December 15, 2022): 101–7. http://dx.doi.org/10.3897/rrpharmacology.8.85918.

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Introduction: Cancer immunotherapy with monoclonal antibodies (mAbs) has become a therapy with great potential nowadays. It is based on the affinity of antibodies to bind to specific molecules, thus inhibiting the growth and spread of cancer. There is a wide variety of mAbs with differentiated mechanisms and enormous clinical benefits. However, different immunotherapeutic alternatives have emerged due to their limitations, such as the long duration of organ toxicity and the inability to penetrate intracellularly. This mini-review will discuss the emerging alternatives of cancer immunotherapies

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Mahheidari, Naimeh, Jamal Rashidiani, Hamid Kooshki, and Khadijeh Eskandari. "An Effort to Making a Colorimitric Nano-Biosensor for Vibrio cholera Detection." Current Nanoscience 16, no. 5 (October 5, 2020): 793–804. http://dx.doi.org/10.2174/1573413716666191230154316.

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Background: Today, nanoparticles hold great promise in biomedical researches and applications including bacteria detection. The rapid and sensitive outcomes of bacteria detection strategies using nanoparticle conjugates become determinative, especially in bacterial outbreaks. In the current research, we focused on detecting V. cholera bacteria and its toxin using a thiocyanate/Au nanoparticle. Thiocyanate adsorbed strongly on the surface of gold nanoparticles and changed the surface by enhancing surface plasmon resonance of gold nanoparticles. Objective: This method is tried to introduce a sim

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Akter, Sultana, Teemu Kustila, Janne Leivo, Gangatharan Muralitharan, Markus Vehniäinen, and Urpo Lamminmäki. "Noncompetitive Chromogenic Lateral-Flow Immunoassay for Simultaneous Detection of Microcystins and Nodularin." Biosensors 9, no. 2 (June 18, 2019): 79. http://dx.doi.org/10.3390/bios9020079.

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Cyanobacterial blooms cause local and global health issues by contaminating surface waters. Microcystins and nodularins are cyclic cyanobacterial peptide toxins comprising numerous natural variants. Most of them are potent hepatotoxins, tumor promoters, and at least microcystin-LR is possibly carcinogenic. In drinking water, the World Health Organization (WHO) recommended the provisional guideline value of 1 µg/L for microcystin-LR. For water used for recreational activity, the guidance values for microcystin concentration varies mostly between 4–25 µg/L in different countries. Current immunoa

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Wrobel, Charles J., Donald C. Wright, Robert L. Dedrick, and Richard J. Youle. "Diphtheria toxin effects on brain-tumor xenografts." Journal of Neurosurgery 72, no. 6 (June 1990): 946–50. http://dx.doi.org/10.3171/jns.1990.72.6.0946.

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✓ A model was developed to determine whether protein-based chemotherapeutic agents can cross the blood-brain barrier and successfully treat brain tumors. The human small-cell lung carcinoma N417D was grown as a solid tumor in the nude rat brain, and diphtheria toxin (DT) was administered intravenously as therapy. Because rat cells lack functional DT receptors and are 1000 to 10,000 times less sensitive to DT than human cells, a therapeutic window exists between the implanted human tumor and the nude rat host. The pharmacokinetic and pharmacodynamic characteristics of DT were defined. Within 6

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Budde, Lihua Elizabeth, Armen Mardiros, Wen-Chung Chang, Xiuli Wang, Carolina Berger, Christine Brown, Stanley R. Riddell, Oliver W. Press, and Stephen J. Forman. "Truncated Cell-Surface CD19 As a Conditional Suicide Switch For Adoptive T Cell Immunotherapy." Blood 122, no. 21 (November 15, 2013): 1660. http://dx.doi.org/10.1182/blood.v122.21.1660.1660.

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Background Modification of T cells with chimeric antigen receptors (CAR) has emerged as a promising treatment modality for human malignancies. However, the potential for insertional mutagenesis and toxicities due to the infused cells have made development of safe Methods for removing transferred cells after treatment an important consideration. In addition, there is a lack of effective commercially available agents which allow for monitoring of CAR expression, tracking, isolating, and eliminating CAR- transduced cells. Therefore, adoptive T cell immunotherapy would benefit from a molecule whic

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Eriksson, Kristina, Margareta Fredriksson, Inger Nordström, and Jan Holmgren. "Cholera Toxin and Its B Subunit Promote Dendritic Cell Vaccination with Different Influences on Th1 and Th2 Development." Infection and Immunity 71, no. 4 (April 2003): 1740–47. http://dx.doi.org/10.1128/iai.71.4.1740-1747.2003.

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ABSTRACT Cholera toxin (CT) is a strong mucosal adjuvant for codelivered antigens, whereas its nontoxic B subunit (CTB) is an efficient mucosal carrier molecule for the generation of immune responses to linked antigens. We investigated the effects of CT and CTB on the immunogenicity of in vitro-treated antigen-pulsed dendritic cells (DC) following intravenous injection into mice. Prior to infusion, DC were pulsed for 90 min with either free ovalbumin (OVA), OVA mixed with CT or CTB, or chemical conjugates of OVA with CT and CTB (OVA-CT and OVA-CTB). DC pulsed with OVA or with OVA and CTB gave

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