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:Autologous T-Cell Therapies in Solid Tumor Malignancies: Current Landscape and Future Opportunities.
Autologous T-Cell Therapies in Solid Tumor Malignancies: Current Landscape and Future Opportunities.
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经过改造的自体T细胞免疫疗法在血液系统恶性肿瘤的治疗中具有变革性意义,已有多种CAR-T 细胞疗法获批用于治疗淋巴瘤、白血病和多发性骨髓瘤。在这些适应症中,治疗已实现高达80%-90%的持久缓解率。由于复杂的肿瘤微环境、抗原异质性以及阻碍实体瘤中抗肿瘤T细胞反应的免疫抑制机制,这些发现在实体瘤恶性肿瘤的临床试验中尚未得到重复。目前正在研究多种策略,并已证明能够成功克服这些障碍。本文概述了自体T细胞疗法的当前格局,特别关注其作为难治性实体瘤恶性肿瘤治疗的应用,重点介绍了正在进行的临床试验中研究的有前景的靶点以及与这些治疗方法相关的毒性。
Modified, autologous T-cell immunotherapies have been transformative in the treatment of hematologic malignancies with several approvals of chimeric antigen receptor T-cell therapies to treat lymphoma, leukemia, and multiple myeloma. Treatment in these settings has resulted in durable response rates as high at 80%-90%.
These findings have not been replicated in clinical trials of solid tumor malignancies because of the complex tumor microenvironment, antigen heterogeneity, and immunosuppressive mechanisms that hinder antitumor T-cell responses in solid tumors. Several strategies are being investigated and have proven successful in overcoming these hurdles.
This paper provides an overview of the current landscape of autologous T-cell therapies, with a particular focus on their use as treatments for refractory solid tumor malignancies, highlighting promising targets being investigated in ongoing clinical trials and toxicities associated with these therapeutic approaches.
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