American Association for Cancer Research
cir-23-0817_supplementary_figure_5_suppsf5.docx (209.75 kB)

Supplementary Figure 5 from The Immune Suppressor IGSF1 as a Potential Target for Cancer Immunotherapy

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journal contribution
posted on 2024-04-02, 07:20 authored by Dong-In Koh, Minki Lee, Yoon Sun Park, Jae-Sik Shin, Joseph Kim, Yea Seong Ryu, Jun Hyung Lee, Seunggeon Bae, Mi So Lee, Jun Ki Hong, Hong-Rae Jeong, Mingee Choi, Seung-Woo Hong, Dong Kwan Kim, Hyun-kyung Lee, Bomi Kim, Yoo Sang Yoon, Dong-Hoon Jin

Target identification was conducted to identify the counter-partner of IGSF1.





The development of first-generation immune-checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 ushered in a new era in anticancer therapy. Although immune-checkpoint blockade therapies have shown clinical success, a substantial number of patients yet fail to benefit. Many studies are under way to discover next-generation immunotherapeutic targets. Immunoglobulin superfamily member 1 (IGSF1) is a membrane glycoprotein proposed to regulate thyroid function. Despite containing 12 immunoglobin domains, a possible role for IGSF1, in immune response, remains unknown. Here, our studies revealed that IGSF1 is predominantly expressed in tumors but not normal tissues, and increased expression is observed in PD-L1low non–small cell lung cancer (NSCLC) cells as compared with PD-L1high cells. Subsequently, we developed and characterized an IGSF1-specific human monoclonal antibody, WM-A1, that effectively promoted antitumor immunity and overcame 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 (PBMC), and syngeneic mouse models, finding additive efficacy in combination with an anti–PD-1 (a well-characterized checkpoint inhibitor). These findings support IGSF1 as an immune target that might complement existing cancer immunotherapeutics.

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