In order to stimulate antigen presentation and T cell activity against cancer, we treated three different tumor models in mice with the monoclonal antibodies anti-CD40 plus anti-CD137 (BiMab). In a subcutaneous transplantable MC38 colon cancer model, there was significant enhancement in the survival of mice following BiMab treatment. Anti-CD40 has shown considerable success against lymphoma in previous studies by other investigators, and we also showed in this study that, in a model of Eμ-Myc lymphoma, there was a statistically significant enhancement of survival of mice following BiMab treatment. Following the success of the BiMab treatment in the previous two models, we wished to determine if it would be successful in a mouse model of multiple myeloma. Firstly, we tested a transplantable model of disease in which multiple myeloma cells derived from Vk*MYC mice were injected intravenously. A minor proportion of anti-CD137 and BiMab treated mice experienced prolongation of life beyond 250 days. Then we tested the therapy in a spontaneously occurring multiple myeloma model, in Vk*MYC transgenic mice. The majority of mice treated survived longer than control mice, although statistical significance was not demonstrated.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.leukres.2014.05.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification of a broad-inhibition influenza neuraminidase antibody from pre-existing memory B cells.
Cell Host Microbe
January 2025
Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, Center for Infectious Disease Research, School of Medicine, Westlake University, Hangzhou, Zhejiang, China; Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China; School of Life Science, Westlake University, Hangzhou, Zhejiang, China. Electronic address:
Identifying broadly reactive B precursor cells and conserved epitopes is crucial for developing a universal flu vaccine. In this study, using influenza neuraminidase (NA) mutant probes, we find that human pre-existing NA-specific memory B cells (MBCs) account for ∼0.25% of total MBCs, which are heterogeneous and dominated by class-unswitched MBCs.
View Article and Find Full Text PDFCo-Stimulatory Bispecific Antibodies Induce Enhanced T Cell Activation and Tumor Cell Killing in Breast Cancer Models.
Front Immunol
December 2021
Antigen Presentation and T/NK Cell Activation Group, DKFZ, Heidelberg, Germany.
Although T cell-recruiting CD3-binding bispecific antibodies (BiMAb) have been proven to be clinically effective for hematologic malignancies, the success of BiMAb targeting solid tumor-associated antigens (TAA) in carcinomas so far remains poor. We reasoned that provision of co-stimulatory BiMAb in combination with αTAA-αCD3 BiMAb would boost T cell activation and proliferative capacity, and thereby facilitate the targeting of weakly or heterogeneously expressed tumor antigens. Various αTAA-αCD3 and αTAA-αCD28 BiMAb in a tetravalent IgG1-Fc based format have been analyzed, targeting multiple breast cancer antigens including HER2, EGFR, CEA, and EpCAM.
View Article and Find Full Text PDFCombination anti-CD137 and anti-CD40 antibody therapy in murine myc-driven hematological cancers.
Leuk Res
August 2014
Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3002, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville 3010, Australia; Department of Immunology, Monash University, Prahran 3181, Australia. Electronic address:
In order to stimulate antigen presentation and T cell activity against cancer, we treated three different tumor models in mice with the monoclonal antibodies anti-CD40 plus anti-CD137 (BiMab). In a subcutaneous transplantable MC38 colon cancer model, there was significant enhancement in the survival of mice following BiMab treatment. Anti-CD40 has shown considerable success against lymphoma in previous studies by other investigators, and we also showed in this study that, in a model of Eμ-Myc lymphoma, there was a statistically significant enhancement of survival of mice following BiMab treatment.
View Article and Find Full Text PDFCross-linking tumor cells with effector cells via CD55 with a bispecific mAb induces beta-glucan-dependent CR3-dependent cellular cytotoxicity.
Eur J Immunol
April 2006
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Complement (C) regulatory proteins decrease the effectiveness of immunotherapeutic anti-cancer antibodies. Bispecific mAb (bi-mAb) that target a tumor antigen and simultaneously inhibit a C regulator increase the effectiveness of such a therapy. Here we investigated the mechanism by which bi-mAb increase tumor cell lysis.
View Article and Find Full Text PDFInhibiting complement regulators in cancer immunotherapy with bispecific mAbs.
Expert Opin Biol Ther
December 2005
Department of Medical Inflammation Research, Lund University, BMC I-11, 221 84 Lund, Sweden.
Although monoclonal antibody (mAb)-mediated immunotherapy of cancer has been proven to be feasible for clinical use, success rates until now have been disappointing. One reason for this might be the overexpression of membrane-bound complement regulatory proteins (mCRPs) by tumour cells. As complement activation is an important effector mechanism induced by therapeutic mAbs, inhibition of complement activation by tumour cells might reduce therapeutic efficacy by decreasing direct complement-mediated lysis as well as complement-dependent cellular cytotoxicity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!