IgA Fc-folate conjugate activates and recruits neutrophils to directly target triple-negative breast cancer cells

Breast Cancer Research and Treatment
Eric D FronteraCecilia L Speyer

Abstract

According to the American Cancer Society, 1 in 8 women in the U.S. will develop breast cancer, with triple-negative breast cancer (TNBC) comprising 15-20% of all breast cancer cases. TNBC is an aggressive subtype due to its high metastatic potential and lack of targeted therapy. Recently, folate receptor alpha (FRA) is found to be expressed on 80% of TNBC with high expression correlating with poor prognosis. In this study, we examined whether binding IgA Fc-folate molecules to FRA receptors on TNBC cells can elicit and induce neutrophils (PMNs), by binding their FcαR1 receptors, to destroy TNBC cells. FRA was analyzed on TNBC cells and binding assays were performed using 3H-folate. Fc-folate was synthesized by linking Fc fragments of IgA via amine groups to folate. Binding specificity and antibody-dependent cellular cytotoxicity (ADCC) potential of Fc-folate to FcαR1 were confirmed by measuring PMN adhesion and myeloperoxidase (MPO) release in a cell-based ELISA. Fc-folate binding to FRA-expressing TNBC cells inducing PMNs to destroy these cells was determined using 51Cr-release and calcein-labeling assays. Our results demonstrate expression of FRA on TNBC cells at levels consistent with folate binding. Fc-folate binds with hig...Continue Reading

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Citations

Sep 29, 2020·Investigational New Drugs·Clinton YamStacy L Moulder
Oct 6, 2020·Frontiers in Nutrition·Ornella I SelminDonato F Romagnolo
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Joana MaiaBruno Costa-Silva

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