CELL INTELLIGENCE · 肿瘤细胞治疗研究

Despite progression-free survival in multiple myeloma (MM) patients extending to 17 years due to contemporary quadruplet induction therapies, there remains a necessity for novel products in the treatment of high-risk patients. BCMA, GPRC5D, FcRH5, SLAMF7, and TACI are the principal chimeric antigen receptor T (CAR-T) cell target molecules, with dual-target treatments under development to enhance treatment efficacy. Ide-cel and cilta-cel are CAR-T cells directed against BCMA, having received approval from the U.S. Food and Drug Administration for relapsed/refractory MM based on the phase 2 KarMMa and CARTITUDE trials, respectively. Research is currently being conducted on the administration of these products in newly diagnosed patients and for maintenance therapy. Additional anti-BCMA targeted medicines, including LCAR-B38M, completely humanized CAR-T (FHVH-T), P-BCMA-ALLO-1, ALLO-715, and anti-BCMA CAR-NK, provide promising treatment options. Moreover, the anti-CD19 Fast-CAR, designed to shorten production time, and PHE885, which possesses in vivo proliferation capability, are regarded as very efficacious. Arlo-cel, developed for the significant target GPRC5D, has demonstrated efficacy compared to conventional treatments. The development of academic CAR-T products such as ARI0002h, HBI0101, eque-cel, zevor-cel, anito-cel, and Sleeping Beauty (utilizing a non-viral vector) have importance due to their accessibility and cost-effectiveness. Real-world data have demonstrated comparable efficacy and safety outcomes in both academic and commercial CAR-T research. CAR-T cell studies are also being undertaken for smoldering MM and amyloid light-chain (AL) amyloidosis. CAR-PRISMM and CAR-HiRiSMM are regarded as extremely effective and safe therapies for patients with high-risk smoldering MM. NXC-201, which targets BCMA, has been developed for AL amyloidosis. Notwithstanding these promising outcomes, numerous difficulties still confront CAR-T therapy. These factors may be related to the tumor, the patient, and/or the CAR-T product. To overcome these issues, new strategies are being implemented, including combination therapy and the incorporation of gamma-secretase inhibitors. In conclusion, CAR-T treatments have evolved into an effective therapy modality and are anticipated to be utilized in earlier treatment phases in the future. The CRISPR gene editing method contributes to future perspectives. G ncel quadruplet ind ksiyon rejimleri sayesinde multipl miyelom (MM) hastalar nda progresyonsuz sa kal m n 17 y la kadar uzad bildirilmesine ra men y ksek riskli hasta pop lasyonunda halen yenilik i tedavi modalitelerine belirgin bir gereksinim bulunmaktad r. BCMA, GPRC5D, FcRH5, SLAMF7 ve TACI, kimerik antijen resept r T h cresi (CAR-T) tedavilerinde ba l ca hedef antijenler olup, etkinli i art rmaya y nelik ift hedefli CAR-T yakla mlar aktif olarak geli tirilmektedir. BCMA y hedefleyen ide-cel ve cilta-cel, s ras yla faz II KarMMa ve CARTITUDE al malar temelinde relaps/refrakter MM i in ABD G da ve la Dairesi onay alm t r. G ncel klinik ara t rmalar, bu r nlerin yeni tan alan hastalarda ve idame tedavisi ba lam nda kullan m potansiyelini de erlendirmeye odaklanmaktad r. Buna ek olarak, LCAR-B38M, tamamen insanla t r lm CAR-T yap lar (FHVH-T), P-BCMA-ALLO-1, ALLO-715 gibi allojeneik CAR-T uygulamalar ve anti-BCMA CAR-NK h creleri, umut vadeden yeni nesil tedavi stratejileri olarak ne kmaktad r. retim s resini k saltmay hedefleyen anti-CD19 Fast-CAR ile in vivo proliferasyon kapasitesine sahip PHE885, y ksek terap tik etkinlik potansiyeli nedeniyle zellikle dikkat ekmektedir. GPRC5D yi hedefleyen arlocel, konvansiyonel tedavilere k yasla anlaml klinik etkinlik g stermi tir. ARI0002h, HBI0101, eque-cel, zevorcel, anito-cel ve viral olmayan vekt r kullanan Sleeping Beauty gibi akademik CAR-T r nlerinin geli tirilmesi, eri ilebilirlik ve maliyet etkinli i a s ndan kritik neme sahiptir. Ger ek ya am verileri, akademik ve ticari CAR-T uygulamalar a