肿瘤细胞治疗研究
英文原题：CAR NK92 Cells Targeting BCMA Can Effectively Kill Multiple Myeloma Cells Both In Vitro and In Vivo.
CAR NK92 Cells Targeting BCMA Can Effectively Kill Multiple Myeloma Cells Both In Vitro and In Vivo.
这些结果表明，局部给予BCMA CAR NK92细胞是治疗MM的一种潜在有前景的策略。
多发性骨髓瘤（MM）是一种由骨髓中浆细胞恶性增殖引起的血液系统恶性肿瘤。在过去十年中，随着新型治疗药物的出现，多发性骨髓瘤（MM）患者的生存结局得到了显著改善。然而，MM仍然是一种无法治愈的肿瘤性浆细胞疾病。此外，几乎所有MM患者都不可避免地因耐药而复发。嵌合抗原受体（CAR）修饰的NK细胞代表了一种有前景的癌症免疫治疗方式。在本研究中，NK92细胞被工程化改造以表达第三代BCMA CAR。在体外，当BCMA CAR工程化NK92细胞与MM细胞系共培养时，其显示出比NK92细胞更高的细胞毒性，并产生更多细胞因子，如IFN-γ和颗粒酶B。此外，当BCMA CAR工程化NK92细胞暴露于从MM患者分离的原代细胞时，其释放的细胞因子量显著更高，并显示出更高的细胞毒性。在MM细胞经硼替佐米处理后，BCMA CAR NK92细胞的细胞毒性增强。此外，BCMA CAR NK92细胞在MM皮下肿瘤模型中表现出强效的抗肿瘤活性。这些结果表明，局部给予BCMA CAR NK92细胞是治疗MM的一种潜在有前景的策略。
Multiple myeloma (MM) is a hematological malignancy caused by malignant proliferation of plasma cells in bone marrow. Over the last decade, the survival outcome of patients with multiple myeloma (MM) has been substantially improved with the emergence of novel therapeutic agents. However, MM remains an incurable neoplastic plasma cell disorder. In addition, almost all MM patients inevitably relapse due to drug resistance. Chimeric antigen receptor (CAR)-modified NK cells represent a promising immunotherapeutic modality for cancer treatment. In this study, NK92 cells were engineered to express the third generation of BCMA CAR. In vitro, BCMA CAR-engineered NK92 cells displayed higher cytotoxicity and produced more cytokines such as IFN-γ and granzyme B than NK92 cells when they were co-cultured with MM cell lines. Furthermore, BCMA CAR-engineered NK92 cells released significantly higher amounts of cytokines and showed higher cytotoxicity when they were exposed to primary cells isolated from MM patients. The cytotoxicity of BCMA CAR NK92 cells was enhanced after MM cells were treated with bortezomib. Additionally, BCMA CAR NK92 cells exhibited potent antitumor activities in subcutaneous tumor models of MM. These results demonstrate that regional administration of BCMA CAR NK92 cells is a potentially promising strategy for treating MM.
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