{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T13:36:50Z","timestamp":1771076210649,"version":"3.50.1"},"reference-count":197,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Multiple myeloma (MM) is a malignant plasma cell disorder that remains incurable for most patients, as persistent clonal evolution drives new mutations which confer MM high-risk signatures and resistance to standard care. The past two decades have significantly refashioned the therapeutic options for MM, especially adoptive T cell therapy contributing to impressive response rate and clinical efficacy. Despite great promises achieved from chimeric antigen receptor T-cell (CAR-T) therapy, the poor durability and severe toxicity (cytokine release syndrome and neurotoxicity) are still huge challenges. Therefore, relapsed\/refractory multiple myeloma (RRMM), characterized by the nature of clinicopathologic and molecular heterogeneity, is frequently associated with poor prognosis. B Cell Maturation Antigen (BCMA) is the most successful target for CAR-T therapy, and other potential targets either for single-target or dual-target CAR-T are actively being studied in numerous clinical trials. Moreover, mechanisms driving resistance or relapse after CAR-T therapy remain uncharacterized, which might refer to T-cell clearance, antigen escape, and immunosuppressive tumor microenvironment. Engineering CAR T-cell to improve both efficacy and safety continues to be a promising area for investigation. In this review, we aim to describe novel tumor-associated neoantigens for MM, summarize the data from current MM CAR-T clinical trials, introduce the mechanism of disease resistance\/relapse after CAR-T infusion, highlight innovations capable of enhanced efficacy and reduced toxicity, and provide potential directions to optimize manufacturing processes.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1050522","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T11:47:11Z","timestamp":1671709631000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Chimeric antigen receptor T-cell therapy for multiple 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