The Society of Surgical Oncology, inc.
The American Society of Breast Surgeons.
Annals of Surgical Oncology

Log in | Register

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

Denise Garcia MD, Patrick Nasarre PhD, Ingrid V. Bonilla BS, Eleanor Hilliard BS, Yuri K. Peterson PhD, Laura Spruill MD, PhD, Anne-Marie Broome PhD, Elizabeth G. Hill PhD, Jason T. Yustein MD, PhD, Shikhar Mehrotra PhD, Nancy Klauber-DeMore MD, FACS
Translational Research and Biomarkers
Volume 26, Issue 13 / December , 2019

Abstract

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 < 0.05) threshold in any of the healthy donors. SVR angiosarcoma tumor growth was inhibited in vivo, evidenced by significant tumor volume reduction in the hSFRP2 mAb-treated group, compared with controls (n = 10, p < 0.001). Likewise, Hs578T triple-negative breast tumors were smaller in the hSFRP2 mAb-treated group compared with controls (n = 10, p < 0.001). The hSFRP2 mAb treatment correlated with an increase in tumor cell apoptosis (n = 11, p < 0.05). Importantly, hSFRP2 mAb treatment was not associated with any weight loss or lethargy.

Conclusion

We present a novel hSFRP2 mAb with therapeutic potential in breast cancer and sarcoma that has no effect on immunogenicity.

Add a comment



0 comment(s)

ANNALS ON SOCIAL MEDIA

@AnnSurgOncol 

Join the conversation!

Follow the journal on Twitter and Facebook

Help to expand the reach of the journal to support the research and practice needs of surgical oncologists and their patients.