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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
用分泌 CD47-SIRPα 检查点阻断剂的 CAR-T 细胞增强抗体依赖性肿瘤杀伤
英文原题：Potentiating antibody-dependent killing of cancers with CAR T cells secreting CD47-SIRPα checkpoint blocker.
查看英文原题
Potentiating antibody-dependent killing of cancers with CAR T cells secreting CD47-SIRPα checkpoint blocker.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
嵌合抗原受体（CAR）T细胞疗法已成功用于治疗造血系统恶性肿瘤，但疾病复发仍是重要问题。为解决这一问题，研究者工程化构建了“Orexi”CAR-T 细胞，使其能够在肿瘤局部高效分泌CD47阻断剂CV1，并与靶向不同抗原的单克隆抗体联合治疗肿瘤。在异种移植模型中，传统CAR-T 细胞与抗体联合具有相加作用，而CAR-T 细胞局部释放CV1可进一步增强这一作用。此外，Orexi CAR分泌的CV1可逆转体外及肿瘤微环境中髓系细胞的免疫抑制作用。局部分泌CD47抑制剂可绕过遍布全身细胞对药物形成的“CD47汇”，并可能避免全身毒性。CAR-T 细胞治疗、局部CD47阻断和靶向不同抗原的抗体联合，可能成为克服各单药治疗局限的组合策略。
展开英文摘要原文
Chimeric antigen receptor (CAR) T-cell therapy has shown success in the treatment of hematopoietic malignancies; however, relapse remains a significant issue. To overcome this, we engineered "Orexi" CAR T cells to locally secrete a high-affinity CD47 blocker, CV1, at the tumor and treated tumors in combination with an orthogonally targeted monoclonal antibody. Traditional CAR T cells plus the antibody had an additive effect in xenograft models, and this effect was potentiated by CAR T-cell local CV1 secretion.
Furthermore, OrexiCAR-secreted CV1 reversed the immunosuppression of myelomonocytoid cells both in vitro and within the tumor microenvironment. Local secretion of the CD47 inhibitor bypasses the CD47 sink found on all cells in the body and may prevent systemic toxicities. This combination of CAR T-cell therapy, local CD47 blockade, and orthogonal antibody may be a combinatorial strategy to overcome the limitations of each monotherapy.
论文信息
- 作者
- Dacek MM、Kurtz KG、Wallisch P、Pierre SA、Khayat S、Bourne CM、Gardner TJ、Vogt KC
- 单位
- Molecular Pharmacology Program, Sloan Kettering Institute, New York, NY.United States
- 期刊
- Blood2023 Apr 20
- 原文标识
- PubMed 36696633 · DOI 10.1182/blood.2022016101
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →