ArticleJCI insight2019
Chemotherapy followed by anti-CD137 mAb immunotherapy improves disease control in a mouse myeloma model.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Regulatory T cells hamper the efficacy of T-cell-engaging bispecific antibody therapy.Haematologica · 2024Article
- What happens to regulatory T cells in multiple myeloma.Cell death discovery · 2023Review
- TCR-independent CD137 (4-1BB) signaling promotes CD8Immunity · 2023Article
- The immune system in multiple myeloma and precursor states: Lessons and implications for immunotherapy and interception.American journal of hematology · 2023Review
- TIGIT inhibition and lenalidomide synergistically promote antimyeloma immune responses after stem cell transplantation in mice.The Journal of clinical investigation · 2023Article
- Depletion of exhausted alloreactive T cells enables targeting of stem-like memory T cells to generate tumor-specific immunity.Science immunology · 2022Article
- Article
- Dendritic cell therapy with CD137L-DC-EBV-VAX in locally recurrent or metastatic nasopharyngeal carcinoma is safe and confers clinical benefit.Cancer immunology, immunotherapy : CII · 2022Article
- Targeting 4-1BB for tumor immunotherapy from bench to bedside.Frontiers in immunology · 2022Review
- Tumor burden limits bispecific antibody efficacy through T cell exhaustion averted by concurrent cytotoxic therapy.Blood cancer discovery · 2021Article
- Biological and Translational Considerations regarding the Recent Therapeutic Successes and Upcoming Challenges for Multiple Myeloma.Cold Spring Harbor perspectives in medicine · 2021Review
- Review
- Ectopic CD137 expression by rhabdomyosarcoma provides selection advantages but allows immunotherapeutic targeting.Oncoimmunology · 2021Article
- Co-stimulatory agonists: An insight into the immunotherapy of cancer.EXCLI journal · 2021Review
- Laboratory Mice - A Driving Force in Immunopathology and Immunotherapy Studies of Human Multiple Myeloma.Frontiers in immunology · 2021Review
- Autologous Stem Cell Transplantation for Myeloma: Cytoreduction or an Immunotherapy?Frontiers in immunology · 2021Article
- TIGIT as an emerging immune checkpoint.Clinical and experimental immunology · 2020Review
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
Immunotherapy holds promise for multiple myeloma (MM) patients but little is known about how MM-induced immunosuppression influences response to therapy. Here, we investigated the impact of disease progression on immunotherapy efficacy in the Vk*MYC mouse model. Treatment with agonistic anti-CD137 (4-1BB) mAbs efficiently protected mice when administered early but failed to contain MM growth when delayed more than three weeks after Vk*MYC tumor cell challenge. The quality of CD8+ T cell response to CD137 stimulation was not altered by the presence of MM, but CD8+ T cell numbers were profoundly reduced at the time of treatment. Our data suggest that an insufficient ratio of CD8+ T cells over MM cells (CD8/MM) accounts for the loss of anti-CD137 mAb efficacy. We established serum M-protein levels prior to therapy as a predictive factor of response. Moreover, we developed an in silico model to capture the dynamic interactions between CD8+ T cells and MM cells. Finally, we explored two methods to improve the CD8/MM ratio: anti-CD137 mAb immunotherapy combined with Treg-depletion or administered after chemotherapy treatment with cyclophosphamide or melphalan efficiently reduced MM burden and prolonged survival. Altogether, our data indicate that consolidation treatment with anti-CD137 mAbs might prevent MM relapse.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.