박소영 (성균관대학교)

한빛사논문

조회174

성균관대학교

Adv. Healthc. Mater., May 21 2024, | https://doi.org/10.1002/adhm.202401270 Bioconjugated Antibody-Trojan Immune Converter Enhance Cancer Immunotherapy with Minimized Toxicity by Programmed Two-Step Immunomodulation of Myeloid Cells

Soyoung Park ¹, Seung Mo Jin ¹, Suhyeon Kim ¹, Ju Hee Cho ¹, JungHyub Hong ², Yong-Soo Bae ², Yong Taik Lim¹

¹SKKU Advanced Institute of Nanotechnology (SAINT), Department of Nano Engineering, School of Chemical Engineering, and Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea.

²Department of Biological Sciences, Science Research Center (SRC) for Immune Research on Non-lymphoid Organ (CIRNO), Department of Biological Science, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea.

S.Y.P. and S.M.J. contributed equally to this work.

CORRESPONDING AUTHOR: Yong Taik Lim

Abstract

Current immune checkpoint blockade therapy (ICBT) predominantly targets T cells to harness the antitumor effects of adaptive immune system. However, the effectiveness of ICBT is reduced by immunosuppressive innate myeloid cells in tumor microenvironments (TMEs). Toll-like receptor 7/8 agonists (TLR7/8a) are often used to address this problem because they can reprogram myeloid-derived suppressor cells (MDSCs) and tumor-associated M2 macrophages, and boost dendritic cell (DC)-based T-cell generation; however, the systemic toxicity of TLR7/8a limits its clinical translation. Here, to address this limitation and utilize the effectiveness of TLR7/8a, this work suggests a programmed two-step activation strategy via Antibody-Trojan Immune Converter Conjugates (ATICC) that specifically targets myeloid cells by anti-SIRPα followed by reactivation of transiently inactivated Trojan TLR7/8a after antibody-mediated endocytosis. ATICC blocks the CD47-SIRPα ("don't eat me" signal), enhances phagocytosis, reprograms M2 macrophages and MDSCs, and increases cross-presentation by DCs, resulting in antigen-specific CD8 ⁺ T-cell generation in tumor-draining lymph nodes and TME while minimizing systemic toxicity. The local or systemic administration of ATICC improves ICBT responsiveness through reprogramming of the immunosuppressive TME, increased infiltration of antigen-specific CD8 ⁺ T cells, and antibody-dependent cellular phagocytosis. These results highlight the programmed and target immunomodulation via ATICC could enhance cancer immunotherapy with minimized systemic toxicities.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-29)
연구진국내 연구진
분야 바이오·의료융합 > 바이오소재

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