한빛사논문
Seokhyeong Go 1#, Mungyo Jung 2,3#, Suyoung Lee 4#, Sangjun Moon 2, Jihye Hong 1, Cheesue Kim 2, Yeonseok Chung 4*, Byung-Soo Kim 1,2,3,5*
1Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, 08826, Republic of Korea.
2School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
3Institute of Engineering Research, Seoul National University, Seoul, 08826, Republic of Korea.
4Laboratory of Immune Regulation, Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
5Institute of Chemical Processes and BioMAX, Seoul National University, Seoul, 08826, Republic of Korea.
#Contributted equally.
*CORRESPONDING AUTHORS: Yeonseok Chung, Byung-Soo Kim
Abstract
Conventional approaches to developing therapeutic cancer vaccines that primarily activate tumor-specific T cells via dendritic cells (DCs) often demonstrate limited efficacy due to the suboptimal activation of these T cells. To address this limitation, here we develop a therapeutic cancer nanovaccine that enhances T cell responses by interacting with both DCs and T cells. The nanovaccine is based on a cancer cell membrane nanoparticle (CCM-MPLA) that utilizes monophosphoryl lipid A (MPLA) as an adjuvant. To allow direct interaction between the nanovaccine and tumor-specific T cells, anti-CD28 antibodies (aCD28) are conjugated onto CCM-MPLA, resulting in CCM-MPLA-aCD28. This nanovaccine activates tumor-specific CD8+ T cells in both presence and absence of DCs. Compared with nanovaccines that interact with either DCs (CCM-MPLA) or T cells (CCM-aCD28), CCM-MPLA-aCD28 induces more potent responses of tumor-specific CD8+ T cells and exhibits a higher antitumor efficacy in tumor-bearing mice. No differences in T cell activation efficiency and therapeutic efficacy are observed between CCM-MPLA and CCM-aCD28. This approach may lead to the development of effective personalized therapeutic cancer vaccines prepared from autologous cancer cells.
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