Foxp3 therapeutic blockade in murine breast cancer models

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

Mar del Plata

Congreso; Reunion Anual de la SAIC; 2016

SAIC

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 of 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