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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.
This article was published in the following journal.
Name: JCI insight
To explore whether CD137-CD137L interaction could induce mouse vascular smooth muscle cells(VSMCs) calcification via P38 MAPK signaling. (1) Mouse VSMCs obtained from 8-week old male C57 mice were cu...
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Drug treatment designed to further diminish the disease toward complete remission following INDUCTION CHEMOTHERAPY. It helps to consolidate the gains during induction chemotherapy and may be followed by MAINTENANCE CHEMOTHERAPY.
Treatment designed to help prevent a relapse of a disease following the successful primary treatments (INDUCTION CHEMOTHERAPY and CONSOLIDATION CHEMOTHERAPY) with a long-term low-dose drug therapy.
Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.
Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, immunotherapy, hyperthermia, etc.) that precedes a necessary second modality of treatment.
Initial drug treatment designed to bring about REMISSION INDUCTION. It is typically a short-term and high-dose drug treatment that is followed by CONSOLIDATION CHEMOTHERAPY and then MAINTENANCE CHEMOTHERAPY.
Allergies Automimmune Disease Human Papillomavirus (HPV) Immunology Vaccine Immunology is the study of immunity and the defence mechanisms of the body. A greater understanding of immunology is needed to develop vaccines, understand ...
Myeloma is a malignant disease of the bone marrow. The features are an excess of abnormal malignant plasma cells in the bone marrow, lytic deposits on an X-ray and abnormal gammaglobulin in the serum. Symptoms include tiredness and bone pain, and t...
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...