Chaiyaporn Boonchalermvichian, Hao Yan, Biki Gupta, Anabel Rubin, Jeanette Baker, Robert S. Negrin
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引用次数: 0
摘要
变异性自然杀伤 T 细胞疗法是一种新兴的癌症免疫疗法平台。这种独特的细胞群对 CD1d 阳性癌症具有固有的细胞毒性,并能诱导宿主 CD8 T 细胞交叉引物,因此是一种很有前景的癌症治疗细胞疗法候选者。大量证据表明,iNKT 细胞可以调节肿瘤微环境中的骨髓单核细胞群,从而改善免疫失调,抑制肿瘤进展。最终,基于 iNKT 细胞的疗法在保持抗肿瘤活性的同时,还能防止移植物抗宿主病(GVHD)。因此,这些生物学特性使 iNKT 细胞成为治疗各种血液恶性肿瘤和可能的实体瘤的 "现成 "疗法。此外,引入嵌合抗原清除剂(CAR)可进一步靶向 iNKT 细胞并增强其功能。我们预计,改进载体设计和其他策略,如与小分子或免疫检查点抑制剂进行组合治疗,可以提高 CAR iNKT 在体内的持久性、功能性和抗肿瘤活性,同时缓解 iNKT 细胞的功能障碍或衰竭。
invariant Natural Killer T cell therapy as a novel therapeutic approach in hematological malignancies
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.