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The Immune Suppressor IGSF1 as a Potential Target for Cancer Immunotherapy
Dong-In Koh1,2, Minki Lee1,2, Yoon Sun Park1,2,3
1Wellmarkerbio Co., Ltd., Seoul, Republic of Korea.
Cancer Immunology Research
|January 30, 2024
Summary
Researchers identified Immunoglobulin superfamily member 1 (IGSF1) as a novel cancer target. An IGSF1-specific antibody, WM-A1, shows promise in enhancing antitumor immunity, potentially overcoming limitations of current immunotherapies.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- First-generation immune-checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 have revolutionized cancer therapy.
- However, a significant portion of patients do not respond to existing ICIs, necessitating the discovery of novel therapeutic targets.
- Immunoglobulin superfamily member 1 (IGSF1), a membrane glycoprotein, has been implicated in thyroid function, with its role in immune response being largely unexplored.
Purpose of the Study:
- To investigate the potential of IGSF1 as a novel immunotherapeutic target in cancer.
- To develop and characterize an antibody against IGSF1 and evaluate its efficacy in promoting antitumor immunity.
- To explore the combination therapy of IGSF1 inhibition with existing immune-checkpoint blockade.
Main Methods:
- Analysis of IGSF1 expression in tumor versus normal tissues and in non-small cell lung cancer (NSCLC) cells with varying PD-L1 expression levels.
- Development and characterization of a human monoclonal antibody (WM-A1) targeting IGSF1.
- In vitro studies using humanized peripheral blood mononuclear cells (PBMCs) and in vivo studies using syngeneic mouse models to assess WM-A1 efficacy.
- Evaluation of combination therapy with an anti-PD-1 antibody.
Main Results:
- IGSF1 is predominantly expressed in tumors and shows increased expression in PD-L1low NSCLC cells compared to PD-L1high cells.
- The developed IGSF1-specific antibody, WM-A1, demonstrated potent antitumor immunity.
- WM-A1 showed significant efficacy in humanized PBMC and mouse models, with additive benefits when combined with anti-PD-1 therapy.
Conclusions:
- IGSF1 represents a promising novel immune target for cancer immunotherapy.
- The IGSF1-specific antibody WM-A1 offers a potential new therapeutic strategy that may overcome limitations of current ICIs.
- Combination therapy involving IGSF1 blockade could enhance treatment outcomes for cancer patients.
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