NK细胞肿瘤免疫治疗技术的挑战

自然杀伤(NK)细胞具有以MHC I 非依赖识别机制和快速杀伤病变细胞能力、低移植物抗宿主反应(GVHD)风险、可采用异体细胞回输、体内存活周期短和无细胞因子风暴等长期和不可预期风险较低等特点和优势，使其在肿瘤免疫治疗中展现出巨大的应用潜力。虽然外周血单个核细胞（PBMC）来源NK细胞相比干细胞来源NK和NK细胞系在安全性和肿瘤杀伤能力上相对更好，但细胞制备技术的效率、稳定性和安全性仍有待完善；NK细胞被认为是较理想的嵌合抗原受体（chimeric antigen receptor，CAR）载体，但外周血来源NK细胞转染效率较低，影响了CAR-NK的研发进程。由于NK细胞来源和培养技术的多样性，使细胞制品的活性不一，虽然NK细胞在抗血液肿瘤治疗中表现相对突出，但对实体瘤的治疗效果仍有待验证。总之，NK细胞应用开发近年已取得显著进步，但仍面临生产技术和临床疗效等诸多挑战。

Challenges on NK cell cancer immunotherapy

Nature killer(NK) cells possess an great potential on cancer immunotherapy without long term potential adverse events and unpredictable risks due to its biological characteristics, including MHC-independent recognition and rapid killing mechanisms to the target cell, using allogenic donor cells without GVHD, short circulation life span and low CRS risks. Although NK cells from PBMC shown an great tumor killing activities and less safety concerns than from other sources including stem cell and NK cell lines, but an efficient and safer protocols for NK cell expansion from PBMC still need to be improved. NK cell is considered as a great vector for chimera antigen receptors (CARs), however low efficiency of DNA transfection on primary NK cells is still the technically bottle neck for CAR-NK application. Clinical trails with NK cell therapy have shown encouraging efficacies on hematologic malignancy, but inconsistent on solid tumors because the NK cells that were produced from variety source cells and different protocols are differ from phenotype and function. In overall, significant progresses have made on NK cell immunotherapy in recent years, but challenges still ahead in term of manufacture and efficacy.