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:Newer generations of multi-target CAR and STAb-T immunotherapeutics: NEXT CART Consortium as a cooperative effort to overcome current limitations.
过继性 T 细胞免疫治疗已成为治疗对传统癌症治疗复发或难治(R/R)患者的重要方法。
过继性 T 细胞免疫疗法已成为治疗传统癌症疗法后复发或难治(R/R)患者的重要方法。嵌合抗原受体(CAR)T 细胞疗法已改善多种血液系统恶性肿瘤的生存结局,但仍存在显著局限,阻碍其在多数癌症中的广泛应用。为推动该领域发展,马德里自治区的六个研究团队组建了“下一代 CART MAD 联盟”(NEXT CART),旨在开发用于 R/R 癌症及预后不良癌症的新型细胞免疫疗法。NEXT CART 汇集马德里多家基础与转化研究团队及医院,共享并协同开展免疫治疗、基因治疗和免疫突触方面的基础研究,以及儿科和成人肿瘤学临床研究。联盟旨在开发新的细胞工程方法和治疗方案,用于 R/R 成人及儿童肿瘤,并在多中心临床试验中评估。本文讨论 T 细胞疗法目前的局限,并提出对未来发展的看法。发展机会包括开发异基因产品、优化 CAR 信号结构域、联合细胞免疫疗法、采用多靶点策略,以及改进TIL(肿瘤浸润淋巴细胞)/T 细胞受体(TCR)疗法。此外,基础研究旨在发现新的肿瘤靶点、肿瘤微环境中影响 CAR 疗效的分子,以及提高免疫细胞与肿瘤细胞间免疫突触效率的策略。我们对当前细胞免疫疗法的展望既强调了其潜力,也指出了仍需创新解决的障碍,以充分发挥其癌症治疗价值。
Adoptive T cellular immunotherapies have emerged as relevant approaches for treating cancer patients who have relapsed or become refractory (R/R) to traditional cancer treatments. Chimeric antigen receptor (CAR) T-cell therapy has improved survival in various hematological malignancies. However, significant limitations still impede the widespread adoption of these therapies in most cancers. To advance in this field, six research groups have created the "NEXT Generation CART MAD Consortium" (NEXT CART) in Madrid's Community, which aims to develop novel cell-based immunotherapies for R/R and poor prognosis cancers. At NEXT CART, various basic and translational research groups and hospitals in Madrid concur to share and synergize their basic expertise in immunotherapy, gene therapy, and immunological synapse, and clinical expertise in pediatric and adult oncology. NEXT CART goal is to develop new cell engineering approaches and treatments for R/R adult and pediatric neoplasms to evaluate in multicenter clinical trials. Here, we discuss the current limitations of T cell-based therapies and introduce our perspective on future developments. Advancement opportunities include developing allogeneic products, optimizing CAR signaling domains, combining cellular immunotherapies, multi-targeting strategies, and improving tumor-infiltrating lymphocytes (TILs)/T cell receptor (TCR) therapy. Furthermore, basic studies aim to identify novel tumor targets, tumor molecules in the tumor microenvironment that impact CAR efficacy, and strategies to enhance the efficiency of the immunological synapse between immune and tumor cells. Our perspective of current cellular immunotherapy underscores the potential of these treatments while acknowledging the existing hurdles that demand innovative solutions to develop their potential for cancer treatment fully.
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