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:IL-7: a potential next-generation adjuvant for immune cell therapies.
基于细胞的免疫疗法,包括CAR-T细胞、TIL(肿瘤浸润淋巴细胞)(TILs)及内源性T细胞产品,已在血液系统恶性肿瘤中产生了前所未有的临床反应,并且目前正积极研究用于实体瘤的治疗。
从CAR-T细胞到TIL(肿瘤浸润淋巴细胞)及内源性T细胞产品,基于细胞的免疫疗法已在血液系统恶性肿瘤中带来前所未有的临床应答,目前也正在积极研究其用于实体瘤的可能性。然而,若干关键挑战仍限制临床获益的持久性和广度。IL-7是一种多效细胞因子,可同时增加淋巴细胞数量并增强其功能。尽管尚未获准临床使用,IL-7已用于620多名成人和儿童患者,适应情形包括加速异基因干细胞移植后的骨髓恢复、逆转HIV或特发性淋巴细胞减少、治疗多种恶性肿瘤以及增强疫苗应答等。IL-7总体耐受性良好,且可持久增加CD4和CD8 T细胞的数量与功能。近年来,IL-7已用于接受CAR-T细胞治疗的多发性骨髓瘤患者、接受检查点抑制剂治疗的尿路上皮癌患者、接受内源性淋巴细胞细胞疗法的患者,以及患有危重症并伴淋巴细胞减少的COVID-19患者。作者均有临床使用IL-7的经验,并讨论IL-7如何有效应对当前限制过继细胞疗法的主要问题。展望未来,我们认为IL-7将成为多种细胞疗法的重要辅助治疗进展,并希望本文推动其在多种临床情境中开展试验。
Cell-based immune therapies ranging from CAR-T cells to tumor infiltrating lymphocytes (TILs) and endogenous T-cell products, have produced unprecedented clinical responses in hematologic malignancies and are currently under active investigation for solid tumors. Nevertheless, several key challenges continue to limit the durability and breadth of clinical benefit. IL-7 is a pleiotropic cytokine that increases both the number and function of lymphocytes. Although not yet clinically approved, IL-7 has been used in over 620 adult and pediatric patients for a variety of reasons including, for example, to hasten bone marrow recovery after allogenic stem cell transplantation, to reverse lymphopenia due to HIV and idiopathic etiologies, to treat patients with various malignancies, and to boost vaccine responses. IL-7 is generally well-tolerated and effective in producing a durable increase in the number and function of CD4 and CD8 T cells. Recently, IL-7 has been used clinically in multiple myeloma patients receiving CAR-T cell therapy, in patients with urothelial cancer who are receiving checkpoint inhibitors, in patients undergoing endogenous lymphocyte cell therapy, and in critically-ill lymphopenic patients with COVID-19. The authors, all of whom have used IL-7 clinically, discuss how IL-7 effectively addresses all the major problems currently limiting adoptive cell therapies. Peering into the future, we believe that IL-7 will be a major advance as an adjuvant treatment in many cell therapies and hope that this commentary will expedite IL-7's testing in multiple clinical settings.
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