Anti-GD2 antibody dinutuximab inhibits triple-negative breast tumor growth by targeting GD2+ breast cancer stem-like cells

• DOI: 10.1136/jitc-2020-001197
• Publication Date: 2021-03-15T15:37:06Z
• Authors: Stanley Ly; Vivek Anand; Fouad El-Dana; Khoa Nguyen; Yiming Cai; Shirong Cai; Helen Piwnica-Worms; Debasish Tripathy; Aysegul A Sahin; Michael Andreeff; Venkata Lokesh Ba...
• Keywords: Triple-negative breast cancer

Background Triple-negative breast cancer (TNBC) is the most aggressive subtype with no effective standard therapy. Breast stem-like cells (BCSCs) in primary TNBCs are reported to be responsible for metastatic spread of disease and resistance chemotherapy, but available therapeutic tools target BCSCs. We previously that ganglioside GD2 highly expressed on BCSCs inhibition its expression hampers TNBC growth. therefore hypothesized anti-GD2 antibody dinutuximab (ch14.18) targets + inhibits Method To test our hypothesis, we first determined via immunohistochemistry frozen tumor samples from patients (n=89). Then, examined effects cell adhesion, migration, mammosphere formation vitro growth vivo using cell-line patient-derived xenograft (PDX) models. Results found was around 60% tumors at variable levels associated worse overall survival (p=0.002). stroma, normal ducts lobules adjacent tissues have shown low or staining, indicating potentially a novel biomarker microenvironment. Treatment significantly decreased adhesion migration MDA-MB-231 SUM159 cells. Moreover, treatment inhibited mTOR signaling, which has been regulated by Dinutuximab also reduced nude mice bearing xenografts. Finally, combination activated natural killer PDX model improved tumor-bearing mice. Conclusions successfully eliminated both Our data provide proof-of-concept criticality demonstrate potential as approach TNBC.