Therapeutic blockade of Foxp3 using gene therapy vectors.

FLAVIA ZANETTI; CAMILA ZUCCATO; MARIELA MORENO AYALA; MARIANELA CANDOLFI; ELISA BAL DE KIER JOFFÉ; GOTTARDO, MARÍA FLORENCIA; ADRIANA SEILICOVICH; ANTONELA ASAD; ALEJANDO JAVIER NICOLA CANDIA

Congreso; Reunion Anual de la SAIC; 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 antitumor vaccines in experimental breast cancer. Although there is controversy over the role of Foxp3 in tumor cells, we found that P60 inhibits survival and 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-2 inhibitor indomethacin, all of which modulate Foxp3 expression in Tregs. Stimulation of LM3 cells with TGF-β and rapamicyn upregulated Foxp3 expression (p