Adoptive T cell Immunotherapy(T细胞免疫治疗综述)

Adoptive T-cell Immunotherapy

过继性T细胞免疫治疗综述（1）

Abstract

摘要

Epstein-Barr virus (EBV) is associated with a range of malignancies involving B-cells, T-cells,natural killer (NK)-cells, epithelial cells and smooth muscle. All of these are associated with the latent life cycles of EBV, but the pattern of latency-associated viral antigens expressed in tumor cells depends on the type of tumor. EBV-specific T cells (EBVSTs) have been explored as prophylaxis and therapy for EBV-associated malignancies for more than two decades. EBVSTs have been most successful as prophylaxis and therapy for post-transplant lymphoproliferative disease (PTLD), which expresses the full array of latent EBV antigens (type 3 latency), in hematopoietic stem cell transplant recipients. While less effective, clinical studies have also demonstrated their therapeutic potential for PTLD post solid organ transplant, and for EBV-associated malignancies such as Hodgkin’s Lymphoma, Non-Hodgkin’s Lymphoma, and nasopharyngeal carcinoma that express a limited array of latent EBV antigens (type 2 latency).

Several approaches are actively being pursued to improve the antitumor activity of EBVSTs including activation and expansion of T cells specific for the EBV antigens expressed in type 2 latency, genetic

approaches to render EBVSTs resistant to the immunosuppressive tumor environment and combination approaches with other immune-modulating modalities. Given the recent advances and renewed interest in cell therapy, we hope that EBVSTs will become an integral part of our treatment armamentarium against EBV-positive malignancies in the near future.

EB病毒涉及到一系列相关的恶性肿瘤如B细胞淋巴瘤，T细胞淋巴瘤，自然杀伤（NK）细胞淋巴瘤、淋巴上皮细胞样癌、平滑肌肉瘤。所有这些都与EB病毒潜伏的生命周期有关，但在肿瘤细胞中，延迟表达的病毒是取决于肿瘤的类型。在近二十多年，EBVCTL（EBVSTs）一直在探索用来对EBV相关的恶性肿瘤的预防和治疗。EBV-CTL最成功的是用于造血干细胞移植受者PTLD(器官移植后淋巴增殖紊乱性疾病的总称,非单一病种)的预防和治疗，即EBV抗原的全排列（3型潜伏期）。虽然疗效不太有效，临床研究也有表现为PTLD后实体器官移植的治疗潜力，与EB病毒—如霍奇金淋巴瘤，非霍奇金淋巴瘤，和相关的恶性肿瘤鼻咽癌表达有限阵列潜伏抗原（类型2延迟）。有几种方法，积极推行提高EBVCTL抗肿瘤活性包括T细胞的活化和对2型表达EBV抗原特异性扩张延迟，使抗肿瘤的免疫抑制EBVCTL遗传途径环境和与其他免疫调节方式的组合方法。鉴于最近的研究进展和细胞免疫新的方向，我们希望EBVCTL在不久的将来将成为我们处理EBV阳性的恶性肿瘤的一个组成部分。