{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T04:27:07Z","timestamp":1792902427513,"version":"4.5.0"},"reference-count":152,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["124052700009-2"],"award-info":[{"award-number":["124052700009-2"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple myeloma (MM) is a clonal malignancy of plasma cells that remains largely incurable despite major advances in proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Chimeric antigen receptor (CAR)-engineered immune cells have transformed the therapeutic landscape, but CAR-T cell therapy faces challenges such as severe cytokine release syndrome (CRS), neurotoxicity, limited persistence, and logistical complexity. In recent years, natural killer (NK) cells have emerged as a promising platform for next-generation cellular immunotherapy, offering innate antitumor activity, a reduced risk of graft-versus-host disease (GvHD), and the feasibility of \u201coff-the-shelf\u201d allogeneic production. This review summarizes current advances in CAR-NK cell therapy for MM, focusing on two major aspects: the diversity of cell sources\u2014including NK-92, peripheral (PB) and cord blood (CB), and induced pluripotent stem cell (iPSC)-derived NK cells\u2014and the expanding repertoire of target antigens such as BCMA (B-cell maturation antigen), NKG2D, CD38, CD70, SLAMF7, CD138, and GPRC5D. We highlight preclinical and early clinical studies demonstrating potent cytotoxicity, favorable safety profiles, and innovative multi-targeting strategies designed to overcome antigen escape and enhance persistence. Emerging clinical data suggest that CAR-NK cell therapy may combine the specificity of CAR recognition with the inherent safety and versatility of NK biology, offering a potential paradigm shift in the treatment of relapsed or refractory MM. Further clinical validation will determine whether CAR-NK cell therapy can achieve durable remission and complement or surpass current CAR-T modalities.<\/jats:p>","DOI":"10.3390\/ijms262211224","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T13:25:27Z","timestamp":1763645127000},"page":"11224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["State of the Art of CAR-NK Cell Therapy in Multiple Myeloma: A Comprehensive Review of Cell Sources and Target Antigens"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6889-6710","authenticated-orcid":false,"given":"Asya","family":"Bastrich","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamilla","family":"Vinogradova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Mokrousova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Efremova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2707-8313","authenticated-orcid":false,"given":"Oleg","family":"Makhnach","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Goldshtein","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41572-024-00529-7","article-title":"Multiple Myeloma","volume":"10","author":"Malard","year":"2024","journal-title":"Nat. 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