Ramos Carlos A, Heslop Helen E, Brenner Malcolm K
Center for Cell and Gene Therapy, Houston Methodist Hospital, Texas Children's Hospital, and Baylor College of Medicine, Houston, Texas 77030.
Dan L. Duncan Cancer Center.
Annu Rev Med. 2016;67:165-83. doi: 10.1146/annurev-med-051914-021702. Epub 2015 Aug 26.
Lymphomas arise from clonal expansions of B, T, or NK cells at different stages of differentiation. Because they occur in the immunocyte-rich lymphoid tissues, they are easily accessible to antibodies and cell-based immunotherapy. Expressing chimeric antigen receptors (CARs) on T cells is a means of combining the antigen-binding site of a monoclonal antibody with the activating machinery of a T cell, enabling antigen recognition independent of major histocompatibility complex restriction, while retaining the desirable antitumor properties of a T cell. Here, we discuss the basic design of CARs and their potential advantages and disadvantages over other immune therapies for lymphomas. We review current clinical trials in the field and consider strategies to improve the in vivo function and safety of immune cells expressing CARs. The ultimate driver of CAR development and implementation for lymphoma will be the demonstration of their ability to safely and cost-effectively cure these malignancies.
淋巴瘤起源于B、T或NK细胞在不同分化阶段的克隆性扩增。由于它们发生在富含免疫细胞的淋巴组织中,因此易于接受抗体和基于细胞的免疫治疗。在T细胞上表达嵌合抗原受体(CAR)是一种将单克隆抗体的抗原结合位点与T细胞的激活机制相结合的方法,能够实现独立于主要组织相容性复合体限制的抗原识别,同时保留T细胞理想的抗肿瘤特性。在此,我们讨论CAR的基本设计及其相对于其他淋巴瘤免疫疗法的潜在优缺点。我们回顾该领域当前的临床试验,并考虑改善表达CAR的免疫细胞体内功能和安全性的策略。淋巴瘤CAR开发和应用的最终驱动力将是证明其有能力安全且经济高效地治愈这些恶性肿瘤。