CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:invariant Natural Killer T cell therapy as a novel therapeutic approach in hematological malignancies.
invariant Natural Killer T cell therapy as a novel therapeutic approach in hematological malignancies.
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恒定自然杀伤T细胞疗法是一种新兴的癌症免疫治疗平台。这一独特的细胞群体是癌症细胞治疗的有前景的候选者,因为它对CD1d阳性癌症具有内在的细胞毒性,以及能够诱导宿主CD8 T细胞交叉致敏。大量证据支持iNKT细胞可以调节肿瘤微环境中的髓单核细胞群体,以改善免疫失调,从而拮抗肿瘤进展。iNKT细胞还可以通过多种机制保护免受移植物抗宿主病(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,同时提供对GVHD的保护。
因此,这些生物学特性使iNKT细胞成为治疗多种血液恶性肿瘤和可能实体瘤的有前景的“现货型”疗法。此外,引入嵌合抗原受体(CAR)可以进一步靶向iNKT细胞并增强功能。
我们预见,改进的载体设计以及其他策略,如与小分子或免疫检查点抑制剂的联合治疗,可以改善CAR iNKT的体内持久性、功能性,并利用抗肿瘤活性,同时减轻iNKT细胞功能障碍或耗竭。
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.
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