Emerging immunotherapeutics in adenocarcinomas: A focus on CAR-T cells.
Emerging immunotherapeutics in adenocarcinomas: A focus on CAR-T cells.
复制标题
DOI：
--
复制
发表时间：
2016
影响因子：
--
通讯作者：
Mahboubeh Yazdanifar;Ru Zhou;P. Mukherjee
中科院分区：
文献类型：
--
作者：
Mahboubeh Yazdanifar;Ru Zhou;P. Mukherjee
超过80%的所有癌症来自上皮细胞，称为癌。腺癌是最常见的癌症类型，由排列在我们主要器官导管上的特化上皮细胞产生。尽管癌症治疗取得了许多进展，但转移性和难治性癌症仍然是第二大死亡原因。免疫治疗提供了潜在的机会，特异性靶向肿瘤细胞和诱导缓解许多癌症患者。已经开发了使用抗体作为拮抗剂或检查点抑制剂/免疫调节剂、肽或细胞疫苗、细胞因子和过继性T细胞疗法的许多疗法。迄今为止，最具创新性的免疫治疗方法是使用工程化T细胞，也称为嵌合抗原受体T细胞（CAR-T细胞）。CAR-T细胞是表达嵌合分子的遗传修饰的幼稚T细胞，所述嵌合分子包含抗肿瘤抗体的抗原识别结构域（scFv）和T细胞受体（TCR）的一个、两个或三个胞内信号传导结构域。当这些工程化的T细胞通过scFv片段识别并结合肿瘤抗原靶标时，信号被发送到CAR的细胞内TCR结构域，导致T细胞活化以变得对肿瘤细胞具有细胞溶解性。CAR-T细胞疗法在某些造血系统恶性肿瘤中取得了巨大成功，但这种成功尚未外推到腺癌。这是由于与腺癌相关的多种因素与造血系统肿瘤不同。尽管CAR-T细胞在靶向多种癌症方面取得了许多进展，但临床试验显示了与这种治疗相关的不良反应和毒性。新的策略尚未设计出来，以管理与CAR-T细胞疗法相关的副作用。在这篇综述中，我们报告了一些正在开发的用于治疗最常见腺癌的有前景的免疫策略，特别强调了未来一代的CAR-T细胞疗法。
More than 80% of all cancers arise from epithelial cells referred to as carcinomas. Adenocarcinomas are the most common type of carcinomas arising from the specialized epithelial cells that line the ducts of our major organs. Despite many advances in cancer therapies, metastatic and treatment-refractory cancers remain the 2nd leading cause of death. Immunotherapy has offered potential opportunities with specific targeting of tumor cells and inducing remission in many cancer patients. Numerous therapies using antibodies as antagonists or checkpoint inhibitors/immune modulators, peptide or cell vaccines, cytokines, and adoptive T cell therapies have been developed. The most innovative immunotherapy approach so far has been the use of engineered T cell, also referred to as chimeric antigen receptor T cells (CAR-T cells). CAR-T cells are genetically modified naïve T cells that express a chimeric molecule which comprises of the antigen-recognition domains (scFv) of an anti-tumor antibody and one, two, or three intracellular signaling domains of the T cell receptor (TCR). When these engineered T cells recognize and bind to the tumor antigen target via the scFv fragment, a signal is sent to the intracellular TCR domains of the CAR, leading to activation of the T cells to become cytolytic against the tumor cells. CAR-T cell therapy has shown tremendous success for certain hematopoietic malignancies, but this success has not been extrapolated to adenocarcinomas. This is due to multiple factors associated with adenocarcinoma that are different from hematopoietic tumors. Although many advances have been made in targeting multiple cancers by CAR-T cells, clinical trials have shown adverse effects and toxicity related to this treatment. New strategies are yet to be devised to manage side effects associated with CAR-T cell therapies. In this review, we report some of the promising immunotherapeutic strategies being developed for treatment of most common adenocarcinomas with particular emphasis on the future generation of CAR-T cell therapy.