Therapeutic blockade of Foxp3 in murine breast cancer models

MARIELA ALEJANDRA MORENO AYALA; ANTONELA SOFIA ASAD; NOELIA CASARES ; MARIANELA CANDOLFI. ; MARIA FLORENCIA GOTTARDO; FLAVIA ZANETTI; JUAN JOSE LASARTE; MERCEDES IMSEN; ELISA BAL DE KIER JOFFÉ; ADRIANA SEILICOVICH

Mar del Plata

Congreso; LXI Reunión de la Sociedad Argentina de Investigación Clínica; 2016

Regulatory T cells (Tregs) have been involved in the relatively low efficacy of antitumor vaccines in cancer patients. Our previous results indicate that prophylactic antitumor dendritic cell (DC) vaccines improve the survival in murine models of breast cancer. However, DC vaccines administered to tumor-bearing mice induce the expansion of Tregs and lack efficacy in this therapeutic setting. We aimed to improve the antitumor effect of DC vaccines using a cell penetrating peptide (P60) that inhibits Foxp3, a transcription factor required for Treg function. Mice bearing established LM3 or 4T1 breast tumors were treated sc with a DC vaccine loaded with tumor cell lysate and stimulated with CpG. Mice were daily treated with ip injections of P60 or a control peptide. We found that although therapeutic DC vaccines alone did not affect tumor growth, P60 alone or in combination with DC vaccines significantly reduced tumor growth rate (p