THERAPEUTIC BLOCKADE OF FOXP3 USING GENE THERAPY VECTORS

ALEJANDRO J. NICOLA CANDIA, ; ANTONELA S. ASAD; ADRIANA SEILICOVICH; MARIELA A. MORENO AYALA; CAMILA ZUCCATO; FLAVIA ZANETTI; MARIA FLORENCIA GOTTARDO; ELISA BAL DE KIER JOFFÉ; MARIANELA CANDOLFI.

Ciudad Autónoma de Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencia (SAIC, SAIB, SAI, SAA, SAB, SAFE, SAFIS, SAH, SAP).; 2017

Our previous results indicate that systemic administration of a cell penetrating peptide (P60) that inhibits Foxp3, a transcription factor required for Treg function, improves the efficacy of antitumorvaccines in experimental breast cancer. Although there is controversy over the role of Foxp3 in tumor cells, we found that P60 inhibits the survival and the release of IL-10 in Foxp3+ breast tumor cells.Here we aimed to evaluate the regulatory pathways that control Foxp3 expression in LM3 breast tumor cells and to develop gene therapy vectors encoding P60. We assessed the effect of recombinant TGF-β, mTOR inhibitor rapamycin and COX-2inhibitor indomethacin, all of which have been shown to modulate Foxp3 expression in Tregs. Stimulation of LM3 cells with TGF-β and rapamicyn upregulated Foxp3 expression (p