Abramson Cancer Center and the Departments of Medicine, Pediatrics, and Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104; email:
Annu Rev Med. 2014;65:333-47. doi: 10.1146/annurev-med-060512-150254. Epub 2013 Nov 20.
Improved outcomes for patients with cancer hinge on the development of new targeted therapies with acceptable short-term and long-term toxicity. Progress in basic, preclinical, and clinical arenas spanning cellular immunology, synthetic biology, and cell-processing technologies has paved the way for clinical applications of chimeric antigen receptor-based therapies. This new form of targeted immunotherapy merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity and long-term persistence provided by cytotoxic T cells. Although this field is still in its infancy, clinical trials have already shown clinically significant antitumor activity in neuroblastoma, chronic lymphocytic leukemia, and B cell lymphoma, and trials targeting a variety of other adult and pediatric malignancies are under way. Ongoing work is focused on identifying optimal tumor targets and on elucidating and manipulating both cell- and host-associated factors to support expansion and persistence of the genetically engineered cells in vivo. The potential to target essentially any tumor-associated cell-surface antigen for which a monoclonal antibody can be made opens up an entirely new arena for targeted therapy of cancer.
癌症患者的治疗效果得到改善取决于新的靶向治疗方法的发展，这些治疗方法具有可接受的短期和长期毒性。在细胞免疫学、合成生物学和细胞处理技术的基础、临床前和临床领域的进展为基于嵌合抗原受体的治疗的临床应用铺平了道路。这种新形式的靶向免疫疗法将单克隆抗体的精确靶向特异性与细胞毒性 T 细胞提供的强大细胞毒性和长期持久性结合在一起。尽管该领域仍处于起步阶段，但临床试验已经在神经母细胞瘤、慢性淋巴细胞白血病和 B 细胞淋巴瘤中显示出具有临床意义的抗肿瘤活性，针对多种其他成人和儿科恶性肿瘤的试验正在进行中。目前的工作重点是确定最佳的肿瘤靶标，并阐明和操纵细胞和宿主相关因素，以支持体内基因工程细胞的扩增和持久性。针对任何可以产生单克隆抗体的肿瘤相关细胞表面抗原进行靶向治疗的潜力为癌症的靶向治疗开辟了一个全新的领域。
