决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Expanding horizons of cancer immunotherapy: hopes and hurdles.
尽管免疫治疗的结果有所改善,尤其是黑色素瘤和非小细胞肺癌(NSCLC)等肿瘤类型,但在预测性生物标志物的识别和更好的管理方面仍存在挑战。
肿瘤存在包括免疫异质性在内的多种异质性,使癌细胞能够在传统抗癌药物治疗期间存活。因此,利用免疫细胞组分克服抗癌药物耐药具有充分依据。利用免疫系统靶向肿瘤细胞已革新癌症治疗。近年来,临床前和临床研究均取得显著进展,有望使癌症患者获益。研究方法:综述过去十年间PubMed、Scopus和Web of Science收录的免疫治疗策略文献,包括免疫检查点抑制剂(ICI)、TIL(肿瘤浸润淋巴细胞)疗法、抗体药物偶联物(ADC)、癌症疫苗、CAR-T细胞疗法及肠道微生物组的作用。结论:免疫治疗结局已有改善,尤其是在黑色素瘤和非小细胞肺癌(NSCLC)等肿瘤中,但预测性生物标志物的识别和治疗管理仍存在挑战。亟需继续研究免疫功能调节因素,如肠道微生物组来源代谢物、新一代ADC及新型生物制剂。总体而言,应持续探索通过策略性药物递送系统优化协同免疫治疗组合,以推动其在癌症患者中的临床前和临床成功。
BACKGROUND: Tumor displays various forms of tumor heterogeneity including immune heterogeneity that allow cancer cells to survive during conventional anticancer drug interventions. Thus, there is a strong rationale for overcoming anticancer drug resistance by employing the components of immune cells. Using the immune system to target tumor cells has revolutionized treatment. Recently, significant progress has been achieved at preclinical and clinical levels to benefit cancer patients. APPROACH: A review of literature from the past ten years across PubMed, Scopus, and Web of Science focused on immunotherapy strategies. These include immune checkpoint inhibitors (ICIs), tumor-infiltrating lymphocyte therapy, antibody-drug conjugates (ADCs), cancer vaccines, CAR T-cell therapy, and the role of the gut microbiome. CONCLUSION: While immunotherapy outcomes have improved, particularly for tumor types such as melanoma and non-small cell lung cancer (NSCLC), challenges persist regarding predictive biomarker identification and better management. Ongoing research on modifiers of immune function like gut microbiome-derived metabolites, next-generation ADCs, and new classes of biologics is warranted. Overall, continued investigation toward optimizing synergistic immunotherapeutic combinations through strategic drug delivery systems is imperative for preclinical and clinical success in cancer patients.
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