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:Chimeric antigen receptor T-cell (CAR T-cell) and tumor-infiltrating lymphocytes (TILs) therapies in gastrointestinal malignancies: review of literature for clinical applications.
胃肠道恶性肿瘤 (GI malignancies) 在历史上一直有着众所周知的黯淡预后。
胃肠道恶性肿瘤长期以来预后极差。主要治疗方式包括免疫治疗、放疗、手术和化疗,可单独使用或联合以增强疗效;但复发和转移率仍然较高。近几十年来,免疫治疗纳入治疗方案后产生了显著影响。在血液系统恶性肿瘤中,CAR-T 细胞作为免疫疗法已显示出抗癌潜力,也为包括结直肠癌在内的实体瘤提供了有希望的治疗选择。近期临床试验显示,CAR-T在胰腺癌、结直肠癌、食管癌、肝细胞癌和胃癌中具有一定疗效。TIL(肿瘤浸润淋巴细胞)疗法也是一种有前景的胃肠道恶性肿瘤免疫治疗方式;设计TIL疗法时,会提取T细胞并根据胃肠道恶性肿瘤特征进行设计。本综述介绍这两种疗法的临床应用,并重点讨论其挑战和可能的应对策略。CAR-T和TIL疗法治疗胰腺癌、结直肠癌、胃癌及肝细胞癌时显示出较好应答,副作用可耐受且处于可接受范围;但免疫抑制性肿瘤微环境(TME)会抑制免疫疗法活性、妨碍疗效,是一项重大挑战。
Gastrointestinal malignancies (GI malignancies) have had a notoriously dismal prognosis throughout history. The primary therapeutic approaches to treat and manage GI malignancies are immunotherapy, radiotherapy, surgery, and chemotherapy, which may include monotherapy or a combination of these therapies to boost the effect. Nevertheless, the recurrence and metastasis rates remain elevated. In recent decades, immunotherapies have had a powerful impact when included in treatment regimens. In hematologic malignancy, chimeric antigen receptor T cells (CAR-T cell) have shown a promising anticancer impact as one of the immunotherapies. It gives a promising treatment option for solid tumors, including colorectal cancers. In recent clinical trials, the CAR-T cells showed a promising effect on pancreatic, colorectal, esophageal, hepatocellular, and gastric cancers. Tumor-infiltrating lymphocyte (TIL) therapy is another immunotherapy option with promising option for GI malignancies. Through the process of designing the TIL therapy, T cells are extracted and designed according to the nature of the GI malignancy. In this review, we addressed the clinical applications of both therapies while highlighting the challenges and possible strategies to overcome them. CAR T-cells and TIL therapies showed good responses with tolerable and acceptable side effects in treating GI malignancies such as pancreatic, colorectal, gastric, and hepatocellular cancers, while the immunosuppressive tumor microenvironment (TME) inhibiting the activity of immunotherapy and impeding its efficacy is a significant challenge.
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