Autor: |
Wenli Yang, Yanyang Pang, Xi Wang, Zhiheng Lai, Yanda Lu, Shaojiang Zheng, Wu Wang |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
Cell Death and Disease, Vol 14, Iss 7, Pp 1-14 (2023) |
Druh dokumentu: |
article |
ISSN: |
2041-4889 |
DOI: |
10.1038/s41419-023-05914-w |
Popis: |
Abstract Despite the great success of CTLA-4 blocking in cancer treatment, the use of anti-CTLA-4 monoclonal antibodies still faces many limitations. Now, immune checkpoint blocking coupled with adoptive cell therapy is gaining much attention. In this paper, we reported a strategy on the basis of anti-CTLA-4 nanobody (Nb)-modified liposomes to improve these obstacles. An Nb36/liposome complex was constructed and utilized as a blocker of the CTLA-4/B7 signal pathway in a combination with dendritic cell (DC)/tumor fusion vaccine to enhance the CD8+ T cell cytokine secretion, activation, proliferation, as well as specific cytotoxicity. Moreover, the CD8+ T cells induced by LPS-Nb36 and DC/tumor fusion vaccine led to higher CD8+ T cell effector function in vivo, which significantly retarded tumor growth and lengthened survival of tumor-bearing mice (HepG2, A549, and MGC-803). Our data demonstrate that the anti-CTLA-4 Nb-modified liposomes in connection with DC/tumor fusion vaccines enhance the CD8+ T cell antitumor activity in vitro and in vivo, and is expected to be an alternative therapy for patients with malignancies that have T cell dysfunction or have poor treatment against anti-CTLA-4 mAb. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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