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
TYRP1 靶向 CAR-T 细胞在临床前黑色素瘤模型中控制肿瘤进展
英文原题：TYRP1 directed CAR T cells control tumor progression in preclinical melanoma models.
查看英文原题
TYRP1 directed CAR T cells control tumor progression in preclinical melanoma models.
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中文摘要
尽管在晚期黑色素瘤中观察到免疫检查点阻断的治疗效果，但许多肿瘤对治疗无反应，这表明需要新的疗法。在此，我们生成了靶向TYRP1的嵌合抗原受体（CAR）T细胞，TYRP1是一种表达于黑色素瘤表面的黑色素瘤分化抗原，包括罕见的肢端和葡萄膜黑色素瘤。TYRP1靶向CAR-T 细胞在体外和体内对人黑色素瘤表现出抗原特异性激活和细胞毒性活性，且不依赖于MHC等位基因及其表达。此外，表达TYRP1靶向TCR的T淋巴细胞对色素正常组织观察到的毒性，在TYRP1靶向CAR-T 细胞中未观察到。抗TYRP1 CAR-T 细胞提供了一种靶向晚期黑色素瘤的新方法，可作为开发类似新型治疗剂的平台，并作为探究黑色素瘤免疫生物学的工具。
展开英文摘要原文
Despite therapeutic efficacy observed with immune checkpoint blockade in advanced melanoma, many tumors do not respond to treatment, representing a need for new therapies.
Here, we have generated chimeric antigen receptor (CAR) T cells targeting TYRP1, a melanoma differentiation antigen expressed on the surface of melanomas, including rare acral and uveal melanomas. TYRP1-targeted CAR T cells demonstrate antigen-specific activation and cytotoxic activity in vitro and in vivo against human melanomas independent of the MHC alleles and expression.
In addition, the toxicity to pigmented normal tissues observed with T lymphocytes expressing TYRP1-targeted TCRs was not observed with TYRP1-targeted CAR T cells. Anti-TYRP1 CAR T cells provide a novel means to target advanced melanomas, serving as a platform for the development of similar novel therapeutic agents and as a tool to interrogate the immunobiology of melanomas.
论文信息
- 作者
- Hackett CS、Hirschhorn D、Tang MS、Purdon TJ、Marouf Y、Piersigilli A、Agaram NP、Liu C
- 第一作者单位
- Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.United States
- 通讯作者单位
- Roswell Park Cancer Center, Buffalo, NY 14203, USA.United States
- 期刊
- Molecular therapy. Oncology2024 Sep 19
- 原文标识
- PubMed 39308793 · DOI 10.1016/j.omton.2024.200862
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