박윤선 (서울아산병원 생명과학연구원, 웰마커바이오)

한빛사논문

조회272

박윤선Yoon Sun Park

서울아산병원 생명과학연구원, 웰마커바이오

Cancer Immunol. Res., Jan 30 2024, | https://doi.org/10.1158/2326-6066.CIR-23-0817 The immune suppressor IGSF1 as a potential target for cancer immunotherapy

Dong-In Koh ^1,2,10, Minki Lee ^1,2,10, Yoon Sun Park^1,2,3,10, Jae-Sik Shin ^1,10, Joseph Kim^1,2,3,10, Yea Seong Ryu^1,2,10, Jun Hyung Lee ¹, Seunggeon Bae¹, Mi So Lee ¹, Jun Ki Hong ¹, Hong Rae Jeong ¹, Mingee Choi ¹, Seung-Woo Hong ¹, Dong Kwan Kim ⁴, Hyun-Kyung Lee ⁵, Bomi Kim ⁶, Yoo Sang Yoon ⁷, Dong-Hoon Jin ^1,8,9,11

¹WellMarker Bio Co., Ltd., Seoul, Republic of Korea

²Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea

³Department of Pharmacology, AMIST, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

⁴Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

⁵Department of Internal medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Inje University Busan Paik Hospital

⁶Department of Pathology Inje University Haeundae Paik Hospital

⁷Department of Thoracic & Cardiovascular Surgery, Busan Paik Hospital, Inje University, Busan

⁸Department of Convergence Medicine, Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea

⁹Department of Pharmacology, University of Ulsan College of Medicine, Seoul, Republic of Korea

¹⁰These authors were equally contributed

¹¹Correspondence: Dong-Hoon Jin

Abstract

The development of first-generation immune checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 ushered in a new era in anticancer therapy. While immune checkpoint blockade therapies have shown clinical success, a significant number of patients yet fail to benefit. According to recent reports, many studies are underway to discover next-generation immunotherapeutic targets. Here, we identified a novel immunotherapeutic target, IGSF1 (immunoglobulin superfamily member 1), by proteome analysis, a membrane glycoprotein proposed to regulate thyroid function. Despite containing 12 immunoglobin domains, a possible role(s) for IGSF1, in immune response, remains unknown. Our studies revealed that IGSF1 is predominantly expressed in tumors but not normal tissues, and increased expression is observed in PD-L1 low NSCLC cells as compared to PD-L1 high cells.Subsequently, we developed and characterized an IGSF1-specific human monoclonal antibody, WM-A1, that effectively promotes anti-tumor immunity and overcomes the limitations of first-generation immune checkpoint inhibitors, likely via a distinct mechanism of action. We further demonstrated high WM-A1 efficacy in humanized peripheral blood mononuclear cells (PBMCs), and syngeneic mouse models, finding synergistic efficacy in combination with an anti-PD-1 antibody (a well-characterized checkpoint inhibitor). These findings support IGSF1 as a novel immune target that might complement existing cancer immunotherapeutics.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-31)
연구진국내 연구진
분야 의약학 > 종양의학

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