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:Application of double-negative T cells in haematological malignancies: recent progress and future directions.
Application of double-negative T cells in haematological malignancies: recent progress and future directions.
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血液系统恶性肿瘤在全球癌症中占很大比例。血液系统恶性肿瘤的高发生率和死亡率造成了沉重的社会负担。异基因造血干细胞移植广泛用于血液系统恶性肿瘤的治疗。
然而,异基因造血干细胞移植后的移植物抗宿主病和复发不可避免。一种新兴的治疗方法——过继性细胞疗法,已被有效用于血液系统恶性肿瘤的治疗。T细胞、自然杀伤(NK)细胞和TIL(肿瘤浸润淋巴细胞)在治疗应用中均具有巨大潜力,而CAR-T(CAR-T)细胞疗法尤其具有潜力,但细胞因子释放综合征和脱靶效应较为常见。亟需有效的抗癌措施。近年来,研究发现双阴性T细胞(CD3 + CD4 - CD8 -)在预防同种异体/异种移植排斥和抑制移植物抗宿主病方面具有巨大潜力。它们还具有以MHC非限制性方式杀伤多种源自血液系统恶性肿瘤的细胞系的显著能力。
此外,健康供者扩增的双阴性T细胞在良好生产规范(GMP)条件下冷冻保存后仍保留其抗肿瘤能力和抑制移植物抗宿主病的能力,表明双阴性T细胞可能能够作为现货型产品使用。在本综述中,我们阐明了双阴性T细胞在治疗血液系统恶性肿瘤中的潜在治疗能力。我们希望将这些细胞开发为血液系统恶性肿瘤的一种新型疗法。
Haematologic malignancies account for a large proportion of cancers worldwide. The high occurrence and mortality of haematologic malignancies create a heavy social burden. Allogeneic haematopoietic stem cell transplantation is widely used in the treatment of haematologic malignancies.
However, graft-versus-host disease and relapse after allogeneic haematopoietic stem cell transplantation are inevitable. An emerging treatment method, adoptive cellular therapy, has been effectively used in the treatment of haematologic malignancies. T cells, natural killer (NK) cells and tumour-infiltrating lymphocytes (TILs) all have great potential in therapeutic applications, and chimeric antigen receptor T (CAR-T) cell therapy especially has potential, but cytokine release syndrome and off-target effects are common.
Efficient anticancer measures are urgently needed. In recent years, double-negative T cells (CD3 + CD4 - CD8 - ) have been found to have great potential in preventing allograft/xenograft rejection and inhibiting graft-versus-host disease. They also have substantial ability to kill various cell lines derived from haematologic malignancies in an MHC-unrestricted manner.
In addition, healthy donor expanded double-negative T cells retain their antitumour abilities and ability to inhibit graft-versus-host disease after cryopreservation under good manufacturing practice (GMP) conditions, indicating that double-negative T cells may be able to be used as an off-the-shelf product. In this review, we shed light on the potential therapeutic ability of double-negative T cells in treating haematologic malignancies.
We hope to exploit these cells as a novel therapy for haematologic malignancies.
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