THERAPEUTIC BLOCKADE OF FOXP3 IN A MURINE BREAST CANCER MODEL

MORENO AYALA M A; GOTTARDO MF; IMSEN M; ASAD ANTONELLA; FLAVIA ZANETTI; ELISA BAL DE KIER JOFFÉ; NOELIA CASARES; JUAN JOSE LASARTE; SEILICOVICH A; CANDOLFI M

Mar del plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2016

Regulatory T cells (Tregs) have been involved in the relativelylow efficacy of antitumor vaccines in cancer patients. Our previousresults 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 inducethe expansion of Tregs and lack efficacy in this therapeutic setting.We aimed to improve the antitumor effect of DC vaccines using acell penetrating peptide (P60) that inhibits Foxp3, a transcriptionfactor required for Treg function. Mice bearing established LM3 or4T1 breast tumors were treated sc with a DC vaccine loaded withtumor cell lysate and stimulated with CpG. Mice were daily treatedwith ip injections of P60 or a control peptide. We found that althoughtherapeutic DC vaccines alone did not affect tumor growth, P60alone or in combination with DC vaccines significantly reducedtumor growth rate (p