基于过继细胞疗法和免疫检查点阻断疗法的实体瘤个性化联合免疫疗法的前景。

Daiki Kato, Tomonori Yaguchi, Takashi Iwata, Kenji Morii, Takayuki Nakagawa, Ryohei Nishimura, Yutaka Kawakami
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引用次数: 21

摘要

免疫检查点阻断(ICB)和抗原受体基因工程T细胞过继细胞疗法(ACT)已被证明对有限数量的实体瘤患者是成功的。对ICB治疗有反应的患者通常患有T细胞炎症性肿瘤。因此,开发将非T细胞炎症肿瘤转化为T细胞炎症肿瘤的策略非常重要。尽管靶向血液系统恶性肿瘤的嵌合抗原受体转导T (CAR-T)细胞治疗显示出持久的临床反应,但基因工程T细胞治疗在实体肿瘤中的成功受到缺乏独特抗原、癌细胞中抗原丢失和实体肿瘤免疫抑制肿瘤微环境(TME)的阻碍。然而,基因工程T细胞具有强大的杀伤活性和细胞因子生产能力,可以诱导抗原扩散并调节非T细胞炎症肿瘤的TME,这些肿瘤对ICB治疗无反应。针对癌症的免疫反应是高度异质性的,不仅在肿瘤类型之间,而且在同一患者内部或同一类型癌症的不同患者之间,这表明应该根据个体患者的免疫状态采用个性化免疫治疗。在此,我们提出了基于ACT和ICB治疗的实体瘤个性化联合免疫治疗的观点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prospects for personalized combination immunotherapy for solid tumors based on adoptive cell therapies and immune checkpoint blockade therapies.

  Immune checkpoint blockade (ICB) and adoptive cell therapies (ACT) with antigen-receptor gene-engineered T cells have been shown to be successful for a limited number of patients with solid tumors. Responders to ICB therapy typically have T cell-inflamed tumors. Thus, it is important to develop strategies that convert non-T cell-inflamed tumors to T cell-inflamed tumors. Although chimeric antigen receptor transduced T (CAR-T) cell therapy targeting hematological malignancies demonstrated durable clinical responses, the success of gene-engineered T cell therapies in solid tumors is hampered by a lack of unique antigens, antigen loss in cancer cells, and the immune-suppressive tumor microenvironment (TME) of solid tumors. However, gene-engineered T cells possess strong killing activity and cytokine production capacity, which can induce antigen spreading and modulate the TME of non-T cell-inflamed tumors seen in non-responders to ICB therapy. Immune responses against cancer are highly heterogeneous, not only between tumor types, but also within a patient or between different patients with the same type of cancer, indicating that personalized immunotherapy should be employed, based on the immune status of the individual patient. Here, we offer our perspective for personalized combination immunotherapy for solid tumors based on ACT and ICB therapies.

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