한빛사 논문
Mungyo Junga, Mikyung Kangb, Byung-Seok Kimc,d, Jihye Hongb, Cheesue Kima, Choong-Hyun Kohc, Garam Choic, Yeonseok Chungc,* and Byung-Soo Kima,b,e,*
aSchool of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
bInterdisciplinary Program for Bioengineering, Seoul National University, Seoul 08826, Republic of Korea
cLaboratory of Immune Regulation, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
dDivision of Life Sciences, College of Life Science and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea
eInstitute of Chemical Processes, Institute of Engineering Research and BioMAX, Seoul National University, Seoul 08826, Republic of Korea
M.J., M.K., and Byung-Seok. K. contributed equally to this work.
*To whom correspondence should be addressed.
Abstract
Despite the clinically proven efficacies of immune checkpoint blockades, including anti-cytotoxic T lymphocyte-associated protein 4 antibody (αCTLA-4), the low response rate and immune-related adverse events (irAEs) in cancer patients represent major drawbacks of the therapy. These drawbacks of αCTLA-4 therapy are mainly due to the suboptimal activation of tumor-specific cytotoxic T lymphocytes (CTLs) and the systemic nonspecific activation of T cells. To overcome such drawbacks, αCTLA-4 is delivered by dendritic cell-derived nanovesicles presenting tumor antigens (DCNV-TAs) that exclusively interact with tumor-specific T cells, leading to selective activation of tumor-specific CTLs. Compared to conventional αCTLA-4 therapy, treatment with αCTLA-4-conjugated DCNV-TAs significantly inhibits tumor growth and reduces irAEs in syngeneic tumor-bearing mice. This study demonstrates that the spatiotemporal presentation of both αCTLA-4 and tumor antigens enables selective activation of tumor-specific T cells and potentiates the antitumor efficacy of αCTLA-4 without inducing systemic irAEs.
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