T cell immunotherapy mediated by dual-affinity aptamer targeted liposome
10.16438/j.0513-4870.2022-1266
- VernacularTitle:双亲和性适配体靶向脂质体介导的T细胞免疫治疗
- Author:
Huan-huan REN
1
;
Guo-ping JIA
1
;
Jing HUANG
1
;
Meng-di WANG
1
;
Ding-ya SUN
1
;
Chao-nan ZHU
2
;
Shan WANG
1
Author Information
1. Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China
2. Department of Gynecology Tumor, Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha 410013, China
- Publication Type:Research Article
- Keywords:
aptamer;
ual-affinity;
T-cell redirection;
immunotherapy;
immune checkpoint
- From:
Acta Pharmaceutica Sinica
2023;58(5):1338-1346
- CountryChina
- Language:Chinese
-
Abstract:
Redirecting immune cells to the tumor cells and enhancing its anti-tumor immune response is a very promising cancer treatment strategy. AS1411 aptamers have high affinity for malignant tumors with high nucleolin expression, and cytotoxic T lymphocyte associated protein 4 (CTLA-4) aptamers can specifically bind to CTLA-4, which is expressed by T cells. In this study, a dual-affinity aptamer targeted liposome (Dat. Lipo) was constructed based on AS1411 aptamer and CTLA-4 aptamer, and its immunotherapeutic effect on T cells was studied. After the aptamer was modified with cholesterol, Dat. Lipo was prepared by instillation method; its effect of redirecting T cells was determined by confocal micrographs; its T cell immunotherapy effect was evaluated by cell counting kit-8 (CCK8) and T cell penetration was evaluated by tumor spheroids. The results showed that compared with liposomes loaded with one type aptamer, Dat. Lipo could effectively promote the redirection of T cells to tumor cells; Dat. Lipo had good biosafety and immunotherapeutic effect on MCF-7 and HepG2 cells in a concentration-dependent manner; Dat. Lipo could also promote T cells to infiltrate into the tumor spheroids and enhance the immunotherapy effect of T cells in different dimensions. In summary, Dat. Lipo can use the high affinity of aptamers to redirect T cells to tumor cells, enhance the effect of immunotherapy, and has a promising application prospect in tumor therapy. This study was approved by the Examination Committee of Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital.
