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:Radiation for hematologic malignancies: from cell killing to immune cell priming.
Radiation for hematologic malignancies: from cell killing to immune cell priming.
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在过去半个世纪中,放疗的作用发生了革命性变化,部分原因在于其目标从直接杀死癌细胞转向激发抗肿瘤免疫反应,从而攻击受照射和未受照射的肿瘤。抗肿瘤免疫的激发依赖于辐射、肿瘤微环境和宿主免疫系统之间的相互作用,这是肿瘤免疫学中一个新兴的概念。虽然放疗与免疫系统的相互作用主要在实体瘤中进行了研究,但我们正开始了解其在血液系统恶性肿瘤中的相互作用。本综述旨在引导读者了解免疫治疗和过继细胞治疗的一些重要近期进展,重点介绍支持将放疗和免疫治疗纳入血液系统恶性肿瘤治疗的最佳现有证据。文中呈现了关于放疗如何与免疫系统“对话”以刺激和增强抗肿瘤免疫反应的证据。放疗的这种促免疫原性作用可与单克隆抗体、细胞因子和/或其他免疫刺激剂联合使用,以增强血液系统恶性肿瘤的消退。
此外,我们将讨论放疗如何通过充当促进CAR-T 细胞植入和活性的“桥梁”来增强细胞免疫疗法的有效性。这些初步研究表明,放疗可能有助于通过与免疫治疗联合靶向受照射和未受照射的病灶,催化从使用化疗密集型治疗向“无化疗”治疗的转变。这一“旅程”为放疗在血液系统恶性肿瘤中的新用途打开了大门,因为它能够启动抗肿瘤免疫反应,从而增强免疫治疗和过继性细胞治疗。
Over the past half-century, the role of radiotherapy has been revolutionized, in part, by a shift from intent to directly kill cancer cells to the goal of priming anti-tumor immune responses that attack both irradiated and non-irradiated tumors. Stimulation of anti-tumor immunity depends on the interplay between radiation, the tumor microenvironment, and the host immune system, which is a burgeoning concept in cancer immunology. While the interplay of radiotherapy and the immune system has been primarily studied in solid tumors, we are beginning to understand this interplay in hematological malignancies.
The intent of this review is to lead readers through some of the important recent advances in immunotherapy and adoptive cell therapy, highlighting the best available evidence in support of incorporating radiation therapy and immunotherapy into the treatment of hematological malignancies.
Evidence is presented regarding how radiation therapy 'converses' with the immune system to stimulate and enhance anti-tumor immune responses. This pro-immunogenic role of radiotherapy can be combined with monoclonal antibodies, cytokines and/or other immunostimulatory agents to enhance the regression of hematological malignancies.
Furthermore, we will discuss how radiotherapy facilitates the effectiveness of cellular immunotherapies by acting as a "bridge" that facilitated CAR T cell engraftment and activity. These initial studies suggest radiotherapy may help catalyze a shift from using chemotherapy-intensive treatment to treatment that is "chemo-free" by combining with immunotherapy to target both the radiated and non-irradiated disease sites.
This "journey" has opened the door for novel uses of radiotherapy in hematological malignancies due to its ability to prime anti-tumor immune responses which can augment immunotherapy and adoptive cell-based therapy.
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