Sharma Rajesh K, Yolcu Esma S, Shirwan Haval
Department of Microbiology and Immunology, Institute for Cellular Therapeutics, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
Expert Rev Vaccines. 2014 Mar;13(3):387-98. doi: 10.1586/14760584.2014.880340.
Tumor associated antigen (TAA)-based therapeutic vaccines have great potential as a safe, practical, and cost-efficient alternative to standard treatments for cancer. Clinical efficacy of TAA-based vaccines, however, has yet to be realized and will require adjuvants with pleiotropic functions on immune cells. Such adjuvants need not only to generate/boost T cell responses, but also reverse intrinsic/extrinsic tumor immune evasion mechanisms for therapeutic efficacy. This review focuses on a novel agonistic ligand, SA-4-1BBL, for 4-1BB costimulatory receptor as an adjuvant of choice because of its ability to: i) serve as a vehicle to deliver TAAs to dendritic cells (DCs) for antigen uptake and cross-presentation to CD8(+) T cells; ii) augment adaptive Th1 and innate immune responses; and iii) overcome various immune evasion mechanisms, cumulatively translating into therapeutic efficacy in preclinical tumor models.
基于肿瘤相关抗原（TAA）的治疗性疫苗作为癌症标准治疗的一种安全、实用且经济高效的替代方案具有巨大潜力。然而，基于TAA的疫苗的临床疗效尚未实现，需要对免疫细胞具有多效功能的佐剂。此类佐剂不仅需要产生/增强T细胞反应，还需要逆转内在/外在肿瘤免疫逃逸机制以实现治疗效果。本综述重点关注一种新型激动剂配体SA-4-1BBL，它作为4-1BB共刺激受体的佐剂是首选，因为它能够：i）作为一种载体将TAA递送至树突状细胞（DC）以摄取抗原并交叉呈递给CD8(+) T细胞；ii）增强适应性Th1和先天免疫反应；iii）克服各种免疫逃逸机制，在临床前肿瘤模型中累积转化为治疗效果。
