Breast cancer is the second leading cause of death among female cancer patients. Human epidermalgrowth factor receptor 2 (HER-2) overexpression is associated with poor prognosis in 15-20% ofbreast cancer patients. Anti-HER-2 antibody (Herceptin) prolongs the survival of the HER-2+ breastcancer patients. However, resistance to Herceptin is a cause for relapse of aggressive, metastaticcancer in these patients. Our earlier studies have demonstrated that PD-L1 blockade enhances theefficacy of HER-2+ breast cancer whole cell vaccine by increasing the infiltration of T cells into thetumor. The goal of the present study is to determine the duration of protective anti-tumor memoryresponses to HER-2+ breast cancer. In this study, we demonstrate the beneficial effect of GPI-anchored cytokine molecules as adjuvants for generating long lasting memory response against HER-2+ as well as HER-2 negative breast cancer in syngeneic tumor models. Female BALB/c mice werechallenged with D2F2/E2 (HER-2 positive) cells or D2F2/E2 transfected with GPI-IL-12 or GPI-GM-CSF. While the wild-type challenged mice developed tumors, the mice challenged with GPI-cytokineexpressing D2F2/E2 cells were protected. Protected mice were re-challenged with D2F2/E2 cells 3months later and D2F2 cells 4 months later. All of the mice challenged with D2F2 (HER-2 negative) orD2F2/E2 were protected. We have observed strong antibody responses against HER-2 and D2F2tumor specific antigens in these mice. Our results show that long lasting protective anti-tumor memoryresponse against D2F2 and D2F2/E2 is generated by vaccination with D2F2/E2 cells expressing GPI-anchored cytokine molecules.
