A Novel CTLA-4 Blocking Strategy Based on Nanobody Enhances the Activity of Dendritic Cell Vaccine-Stimulated Antitumor Cytotoxic T Lymphocytes
Cell death and disease(2023)
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.
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Key words
Preclinical research,Tumour immunology,Life Sciences,general,Biochemistry,Cell Biology,Immunology,Cell Culture,Antibodies
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