Abstract
Abstract P3-08-30: Development of humanized anti-FABP4 monoclonal antibodies for potential treatment of breast cancer
Clinical cancer research, Vol.31(12_Supplement), pp.P3-P3-08-30
06/13/2025
DOI: 10.1158/1557-3265.SABCS24-P3-08-30
Abstract
Breast cancer is the most common cancer in women diagnosed in the U.S. and worldwide. Obesity increases breast cancer risk without clear underlying molecular mechanisms. Our studies demonstrate that circulating adipose fatty acid binding protein (A-FABP, or FABP4) links obesity-induced dysregulated lipid metabolism and breast cancer risk, thus potentially offering a new target for breast cancer treatment. We immunized FABP4 knockout mice with recombinant human FABP4 and screened hybridoma clones with specific binding to FABP4. The potential effects of antibodies on breast cancer cells in vitro were evaluated using migration, invasion, and limiting dilution assays. Tumor progression in vivo was evaluated in various types of tumorigenesis models including C57BL/6 mice, Balb/c mice, and SCID mice. We identified over 30 clones which specifically bound to FABP4. One clone, named 12G2, was shown to significantly inhibit mammary tumor growth. After further confirming the therapeutic efficacy of the chimeric 12G2 monoclonal antibody consisting of mouse variable regions and human IgG1 constant regions, 16 humanized 12G2 monoclonal antibody variants were generated by grafting its complementary determining regions to selected human germline sequences. Humanized V9 monoclonal antibody showed consistent results in inhibiting mammary tumor growth and metastasis by affecting tumor cell mitochondrial metabolism. Thus, our data suggest that targeting FABP4 with humanized monoclonal antibodies represents a novel strategy for the treatment of breast cancer and possibly other obesity-associated diseases.
Citation Format: Bing Li. Development of humanized anti-FABP4 monoclonal antibodies for potential treatment of breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-08-30.
Details
- Title: Subtitle
- Abstract P3-08-30: Development of humanized anti-FABP4 monoclonal antibodies for potential treatment of breast cancer
- Creators
- Bing Li
- Resource Type
- Abstract
- Publication Details
- Clinical cancer research, Vol.31(12_Supplement), pp.P3-P3-08-30
- DOI
- 10.1158/1557-3265.SABCS24-P3-08-30
- ISSN
- 1557-3265
- eISSN
- 1557-3265
- Publisher
- AMER ASSOC CANCER RESEARCH
- Language
- English
- Date published
- 06/13/2025
- Academic Unit
- Pathology; Surgery
- Record Identifier
- 9984843241302771
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