PDF(Pubmed)
Abstract：
Invariant Natural Killer T cell therapy is an emerging platform of immunotherapy for cancer treatment. This unique cell population is a promising candidate for cell therapy for cancer treatment because of its inherent cytotoxicity against CD1d positive cancers as well as its ability to induce host CD8 T cell cross priming. Substantial evidence supports that iNKT cells can modulate myelomonocytic populations in the tumor microenvironment to ameliorate immune dysregulation to antagonize tumor progression. iNKT cells can also protect from graft-versus-host disease (GVHD) through several mechanisms, including the expansion of regulatory T cells (Treg). Ultimately, iNKT cell-based therapy can retain antitumor activity while providing protection against GVHD simultaneously. Therefore, these biological properties render iNKT cells as a promising \"off-the-shelf\" therapy for diverse hematological malignancies and possible solid tumors. Further the introduction of a chimeric antigen recetor (CAR) can further target iNKT cells and enhance function. We foresee that improved vector design and other strategies such as combinatorial treatments with small molecules or immune checkpoint inhibitors could improve CAR iNKT in vivo persistence, functionality and leverage anti-tumor activity along with the abatement of iNKT cell dysfunction or exhaustion.
摘要：
不变自然杀伤T细胞疗法是用于癌症治疗的免疫疗法的新兴平台。这种独特的细胞群是用于癌症治疗的细胞疗法的有希望的候选者,因为其针对CD1d阳性癌症的固有细胞毒性以及其诱导宿主CD8T细胞交叉引发的能力。大量证据支持iNKT细胞可以调节肿瘤微环境中的粒单核细胞群体以改善免疫失调从而拮抗肿瘤进展。iNKT细胞还可以通过几种机制保护移植物抗宿主病(GVHD),包括调节性T细胞(Treg)的扩增。最终,基于iNKT细胞的疗法可以保留抗肿瘤活性,同时提供针对GVHD的保护。因此,这些生物学特性使iNKT细胞成为多种血液系统恶性肿瘤和可能的实体瘤的“现成”疗法。此外,嵌合抗原受体(CAR)的引入可以进一步靶向iNKT细胞并增强功能。我们预计，改进的载体设计和其他策略，如小分子或免疫检查点抑制剂的组合治疗可以提高CARiNKT的体内持久性。功能和利用抗肿瘤活性以及减少iNKT细胞功能障碍或耗尽。
