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:H1Innovative approaches to combat anti-cancer drug resistance: Targeting lncRNA and autophagy.
本综述总结了在接受不同免疫治疗方式(包括单克隆抗体、小分子抑制剂、癌症疫苗和 CAR-T 细胞)治疗的癌症患者中报道的重要预测性 ncRNA 生物标志物。
背景:由于个体遗传特征、肿瘤微环境复杂性及表观遗传致癌机制存在差异,建立标准化的免疫治疗临床预测生物标志物仍具挑战。正文:早期监测关键非编码RNA(ncRNA)生物标志物可能有助于预测癌症免疫治疗疗效,并建立标准化的ncRNA预测指标。例如,接受抗PD-1治疗的非小细胞肺癌患者血浆miR-125b-5p水平较低可预测较佳结局;接受CAR-T淋巴细胞(CAR-T)治疗的结直肠癌患者血浆miR-153水平可指示T细胞杀伤活化;miR-148a-3p和miR-375水平可能预测B细胞急性淋巴细胞白血病患者对CAR-T治疗的有利应答。接受GPC3肽疫苗的癌症患者血清miR-1228-5p、miR-193a-5p和miR-375-3p据报道可预测较佳应答和更长总生存期。因此,亟需进一步研究,以明确可能用于早期预测免疫治疗临床应答的关键ncRNA生物标志物。结论:本综述总结了接受不同免疫治疗(包括单克隆抗体、小分子抑制剂、癌症疫苗和CAR-T细胞)患者中已报道的重要ncRNA预测标志物,并简要讨论未来方向,包括如何优化免疫调节ncRNA作为预测工具和治疗靶点的技术方案。
BACKGROUND: To date, standardizing clinical predictive biomarkers for assessing the response to immunotherapy remains challenging due to variations in personal genetic signatures, tumour microenvironment complexities and epigenetic onco-mechanisms. MAIN BODY: Early monitoring of key non-coding RNA (ncRNA) biomarkers may help in predicting the clinical efficacy of cancer immunotherapy and come up with standard predictive ncRNA biomarkers. For instance, reduced miR-125b-5p level in the plasma of non-small cell lung cancer patients treated with anti-PD-1 predicts a positive outcome. The level of miR-153 in the plasma of colorectal cancer patients treated with chimeric antigen receptor T lymphocyte (CAR-T) cell therapy may indicate the activation of T-cell killing activity. miR-148a-3p and miR-375 levels may forecast favourable responses to CAR-T-cell therapy in B-cell acute lymphoblastic leukaemia. In cancer patients treated with the GPC3 peptide vaccine, serum levels of miR-1228-5p, miR-193a-5p and miR-375-3p were reported as predictive biomarkers of good response and improved overall survival. Therefore, there is a critical need for further studies to elaborate on the key ncRNA biomarkers that have the potential to predict early clinical responses to immunotherapy. CONCLUSIONS: This review summarises important predictive ncRNA biomarkers that were reported in cancer patients treated with different immunotherapeutic modalities including monoclonal antibodies, small molecule inhibitors, cancer vaccines and CAR-T cells. In addition, a concise discussion on forthcoming perspectives is provided, outlining technical approaches for the optimal utilisation of immune-modulatory ncRNA biomarkers as predictive tools and therapeutic targets.
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