Pulè Martin A, Straathof Karin C, Dotti Gianpietro, Heslop Helen E, Rooney Cliona M, Brenner Malcolm K
Center for Cell and Gene Therapy, Baylor College of Medicine, 6621 Fannin MC3-3320, Houston, TX 77030, USA.
Mol Ther. 2005 Nov;12(5):933-41. doi: 10.1016/j.ymthe.2005.04.016. Epub 2005 Jun 23.
The transduction of primary T cells to express chimeric T cell receptors (cTCR) for redirected targeting of tumor cells is an attractive strategy for generating tumor-specific T cells for adoptive therapy. However, tumor cells rarely provide costimulatory signals and hence cTCRs that transmit just a CD3zeta signal can only initiate target cell killing and interferon-gamma release and fail to induce full activation. Although incorporation of a CD28 component results in IL-2 release and limited proliferation, T cell activation remains incomplete. OX40 transmits a potent and prolonged T cell activation signal and is crucial for maintaining an immunological response. We hypothesize that the CD28-OX40-CD3zeta tripartite cytoplasmic domain will provide a full complement of activation, proliferation, and survival signals for enhanced anti-tumor activity.
将原代T细胞转导以表达嵌合T细胞受体（cTCR）用于重定向靶向肿瘤细胞，是一种为过继性治疗生成肿瘤特异性T细胞的有吸引力的策略。然而，肿瘤细胞很少提供共刺激信号，因此仅传递CD3ζ信号的cTCR只能启动靶细胞杀伤和干扰素-γ释放，而无法诱导完全激活。尽管加入CD28成分会导致IL-2释放和有限的增殖，但T细胞激活仍不完全。OX40传递强大且持久的T细胞激活信号，对维持免疫反应至关重要。我们假设，CD28-OX40-CD3ζ三联体胞质结构域将提供完整的激活、增殖和存活信号补充，以增强抗肿瘤活性。
