Ruella Marco, June Carl H
Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Curr Hematol Malig Rep. 2016 Oct;11(5):368-84. doi: 10.1007/s11899-016-0336-z.
Genetic redirection of T lymphocytes allows us to unleash these potent cellular immune effectors against cancer. Chimeric antigen receptor (CAR) T cells are the best-in-class example that genetic engineering of T cells can lead to deep and durable responses, as has been shown in several clinical trials for CD19+ B cell malignancies. As a consequence, in the last few years, several academic institutions and commercial partners have started developing anti-CD19 CAR T cell products. Although most of these T cell products are highly effective in vivo, basic differences among them can generate different performance characteristics and thereby impact their long-term clinical outcome. Several strategies are being implemented in order to solve the current open issues of CART19 therapy: (i) increasing efficacy against indolent B cell leukemias and lymphomas, (ii) avoiding or preventing antigen-loss relapses, (iii) reducing and managing toxicity, and (iv) bringing this CART therapy to routine clinical practice. The field of CART therapies is thriving, and exciting new avenues are opening for both scientists and patients.
对T淋巴细胞进行基因重定向,使我们能够利用这些强大的细胞免疫效应器对抗癌症。嵌合抗原受体(CAR)T细胞就是一个典型例子,T细胞的基因工程能够引发深度且持久的反应,这在针对CD19+B细胞恶性肿瘤的多项临床试验中已得到证实。因此,在过去几年里,几家学术机构和商业合作伙伴已开始研发抗CD19 CAR T细胞产品。尽管这些T细胞产品中的大多数在体内都非常有效,但它们之间的基本差异可能会产生不同的性能特征,从而影响其长期临床结果。为了解决当前CAR T19疗法存在的开放性问题,正在实施几种策略:(i)提高对惰性B细胞白血病和淋巴瘤的疗效,(ii)避免或预防抗原丢失复发,(iii)减少和管理毒性,以及(iv)将这种CAR T疗法应用于常规临床实践。CAR T疗法领域正在蓬勃发展,为科学家和患者都开辟了令人兴奋的新途径。