Development of a Novel Humanized Monoclonal Antibody to Secreted Frizzled-Related Protein-2 That Inhibits Triple-Negative Breast Cancer and Angiosarcoma Growth In Vivo

• Published in: Annals of surgical oncology 2019-12, Vol.26 (13), p.4782-4790
• Main Authors: Garcia, Denise, Nasarre, Patrick, Bonilla, Ingrid V., Hilliard, Eleanor, Peterson, Yuri K., Spruill, Laura, Broome, Anne-Marie, Hill, Elizabeth G., Yustein, Jason T., Mehrotra, Shikhar, Klauber-DeMore, Nancy
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ANGIOGENESIS; Animals; Antibodies, Monoclonal, Humanized - biosynthesis; Antibodies, Monoclonal, Humanized - pharmacology; APOPTOSIS; Breast cancer; Breast carcinoma; CARCINOMAS; Cell Proliferation; Female; Frizzled protein; Frizzled-related protein; Hemangiosarcoma - drug therapy; Hemangiosarcoma - metabolism; Hemangiosarcoma - pathology; Humans; Immunogenicity; IMMUNOGLOBULINS; Lymphocytes T; MAMMARY GLANDS; Medicine; Medicine & Public Health; Membrane Proteins - immunology; MICE; Mice, Nude; MONOCLONAL ANTIBODIES; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Oncology; Sarcoma; SARCOMAS; Surgery; Surgical Oncology; Translational Research and Biomarkers; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; TUMOR CELLS; Tumor Cells, Cultured; Tumors; Xenograft Model Antitumor Assays
• ISSN: 1068-9265; 1534-4681; 1534-4681
• DOI: 10.1245/s10434-019-07800-2

Background We previously reported that secreted frizzled-related protein-2 (SFRP2) is expressed in a variety of tumors, including sarcoma and breast carcinoma, and stimulates angiogenesis and inhibits tumor apoptosis. Therefore, we hypothesized that a humanized SFRP2 monoclonal antibody (hSFRP2 mAb) would inhibit tumor growth. Methods The lead hSFRP2 antibody was tested against a cohort of 22 healthy donors using a time course T-cell assay to determine the relative risk of immunogenicity. To determine hSFRP2 mAb efficacy, nude mice were subcutaneously injected with SVR angiosarcoma cells and treated with hSFRP2 mAb 4 mg/kg intravenously every 3 days for 3 weeks. We then injected Hs578T triple-negative breast cells into the mammary fat pad of nude mice and treated for 40 days. Control mice received an immunoglobulin (Ig) G1 control. The SVR and Hs578T tumors were then stained using a TUNEL assay to detect apoptosis. Results Immunogenicity testing of hSFRP2 mAb did not induce proliferative responses using a simulation index (SI) ≥ 2.0 ( p