CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Engaging stemness improves cancer immunotherapy.
Engaging stemness improves cancer immunotherapy.
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肿瘤微环境(TME)中的瘤内免疫细胞促进癌症干细胞(CSCs)的干性。CSCs促进肿瘤进展、复发和免疫治疗耐药。癌症干性诱导CSCs中新抗原和新特性的表达,为靶向免疫治疗创造了机会。分离干细胞样T细胞或在T细胞克隆型中保留干性的策略可产生抗耗竭T细胞,这些细胞在过继性细胞治疗后具有优越的再扩增能力和持久反应。干细胞来源的NK细胞可能成为下一代NK细胞免疫治疗产品。在此,我们综述了干性因子调节TME免疫编辑的机制,并总结了CSCs在免疫治疗方案开发中的潜力,包括CAR-T 细胞、CAR-NK细胞、癌症疫苗和单克隆抗体。我们讨论了天然或基因工程干细胞样T细胞以及干细胞来源的NK细胞对肿瘤细胞增强的细胞毒性。最后,我们对可能提高这些新型过继性细胞产品靶向免疫抑制性TME的治疗疗效的方法提供了展望。
Intra-tumoral immune cells promote the stemness of cancer stem cells (CSCs) in the tumor microenvironment (TME). CSCs promote tumor progression, relapse, and resistance to immunotherapy. Cancer stemness induces the expression of neoantigens and neo-properties in CSCs, creating an opportunity for targeted immunotherapies.
Isolation of stem-like T cells or retaining stemness in T clonotypes strategies produces exhaustion-resistance T cells with superior re-expansion capacity and long-lasting responses after adoptive cell therapies. Stem cells-derived NK cells may be the next generation of NK cell products for immunotherapy.
Here, we have reviewed mechanisms by which stemness factors modulated the immunoediting of the TME and summarized the potentials of CSCs in the development of immunotherapy regimens, including CAR-T cells, CAR-NK cells, cancer vaccines, and monoclonal antibodies.
We have discussed the natural or genetically engineered stem-like T cells and stem cell-derived NK cells with increased cytotoxicity to tumor cells.
Finally, we have provided a perspective on approaches that may improve the therapeutic efficacy of these novel adoptive cell-based products in targeting immunosuppressive TME.
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