Despite the success of passive immunotherapy with monoclonal antibodies (mAbs), many lymphoma patients eventually relapse. Induction of an adaptive immune response may elicit active and long-lasting antitumor immunity, thereby preventing or delaying recurrence. Immunomodulating mAbs directed against immune cell targets can be used to enhance the immune response to achieve efficient antitumor immunity. Anti-CD137 agonistic mAb has demonstrated antitumor efficacy in various tumor models and has now entered clinical trials for the treatment of solid tumors. Here, we investigate the therapeutic potential of anti-CD137 mAb in lymphoma. We found that human primary lymphoma tumors are infiltrated with CD137+ T cells. We therefore hypothesized that lymphoma would be susceptible to treatment with anti-CD137 agonistic mAb. Using a mouse model, we demonstrate that anti-CD137 therapy has potent antilymphoma activity in vivo. The antitumor effect of anti-CD137 therapy was mediated by both natural killer (NK) and CD8 T cells and induced long-lasting immunity. Moreover, the antitumor activity of anti-CD137 mAb could be further enhanced by depletion of regulatory T cell (T(regs)). These results support the evaluation of anti-CD137 therapy in clinical trials for patients with lymphoma.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765679 | PMC |
| http://dx.doi.org/10.1182/blood-2009-05-223958 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Photothermal therapy co-localized with CD137 agonism improves survival in an SM1 melanoma model without hepatotoxicity.
Nanomedicine (Lond)
October 2024
Integrated Biomedical Sciences Program, School of Medicine & Health Sciences, George Washington University, WA 20037, USA.
Article Synopsis
- The study combines Prussian Blue nanoparticles (PBNPs) with αCD137 antibodies to create a new anti-tumor treatment platform for melanoma.
- These αCD137-PBNPs maintain their therapeutic properties and were tested for effectiveness and safety in mice with tumors.
- Results showed that mice treated with the αCD137-PBNP-PTT had a much better survival rate (50%) and no liver toxicity compared to other treatments.
Enhanced IL-15-mediated NK cell activation and proliferation by an ADAM17 function-blocking antibody involves CD16A, CD137, and accessory cells.
J Immunother Cancer
July 2024
Department of Veterinary and Biomedical Sciences, University of Minnesota, Minneapolis, Minnesota, USA
Background: Natural killer (NK) cells are being extensively studied as a cell therapy for cancer. These cells are activated by recognition of ligands and antigens on tumor cells. Cytokine therapies, such as IL-15, are also broadly used to stimulate endogenous and adoptively transferred NK cells in patients with cancer.
View Article and Find Full Text PDFShort-term cultured tumor fragments to study immunotherapy combinations based on CD137 (4-1BB) agonism.
Oncoimmunology
July 2024
Immunology, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
Biomarkers for cancer immunotherapy are an unmet medical need. The group of Daniela Thommen at the NKI recently reported on novel methodologies based on short-term cultures of patient-derived tumor fragments whose cytokine concentrations in the supernatants and activation markers on infiltrating T cells were associated with clinical response to PD-1 blockade. We set up a similar culture technology with tumor-derived fragments using mouse tumors transplanted into syngeneic immunocompetent mice to test an agonist anti-CD137 mAb and its combinations with anti-PD-1 and/or anti-TGF-β.
View Article and Find Full Text PDFFinal results of urelumab, an anti-CD137 agonist monoclonal antibody, in combination with cetuximab or nivolumab in patients with advanced solid tumors.
J Immunother Cancer
March 2024
Memorial Sloan Kettering Cancer Center, New York, New York, USA
Background: Resistance to immune checkpoint inhibitors and targeted treatments for cancer is common; thus, novel immunotherapy agents are needed. Urelumab is a monoclonal antibody agonist that binds to CD137 receptors expressed on T cells. Here, we report two studies that evaluated urelumab in combination with cetuximab or nivolumab in patients with select, advanced solid tumors.
View Article and Find Full Text PDFA bispecific anti-PD-1 and PD-L1 antibody induces PD-1 cleavage and provides enhanced anti-tumor activity.
Oncoimmunology
February 2024
Compass Therapeutics Inc, Boston, MA, USA.
Combinatorial strategies, such as targeting different immune checkpoint receptors, hold promise to increase the breadth and duration of the response to cancer therapy. Here we describe the preclinical evaluation of CTX-8371, a protein construct which combines PD-1 and PD-L1 targeting in one bispecific, tetravalent antibody. CTX-8371 matched or surpassed the activity of anti-PD-1 and PD-L1 benchmark antibodies in several T cell activation assays and outperformed clinically approved benchmarks in the subcutaneous MC38 colon and the B16F10 lung metastasis mouse tumor models.
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!