Abstract 2545: Antitumor efficacy of Type I polarized dendritic cells in combination with immune checkpoint blockade in a preclinical model of breast cancer

Abstract

Abstract Breast cancer is the most commonly diagnosed cancer and a major cause of cancer death among women. Our group has shown progressive loss of the anti-HER2 Th1 immune response in HER2 positive breast cancer patients and administration of peptide-pulsed Type I polarized dendritic cell (DC1) vaccine induced strong anti-HER2 immune response with pathologic complete response rate (pCR) in DCIS (ductal carcinoma in situ) and early invasive breast cancer (IBC). Within the tumor microenvironment, presence of multiple factors, including expression of co-inhibitory immune checkpoint signals has been shown to inhibit anti-tumor immune responses and preventing complete tumor regression. Hence, there is a need to develop strategies that disrupt these negative regulators in the tumor microenvironment in order to achieve robust anti-tumor immune responses. In this study, we investigated whether blockade of immune checkpoints, PD-1 or PD-L1 in combination with DC1 vaccine enhance anti-tumor immune response in a preclinical model of HER2 positive TUBO breast cancer. Balb/c mice received TUBO cells subcutaneously on day 0. Two different treatment regimens were followed to examine anti-tumor efficacy. For regimen-1, TUBO- bearing mice received three doses of p66 (MHC class I) peptide-pulsed DC1 vaccine starting on day 7 at weekly intervals concurrently with intraperitoneal injection of anti-PD-1 or anti-PD-L1 monoclonal antibodies. For regimen-2, starting on day 7 mice received six doses of HER2 specific p66 peptide- pulsed DC1 vaccine twice a week. Monoclonal checkpoint antibodies were given after the last dose of DC1 vaccine. Mice that received DC1 vaccine followed by treatment with anti-PD-1 or anti-PD-L1 monoclonal checkpoint antibodies had significant delay in tumor growth compared to the mice that received DC1 or checkpoint antibodies alone. However, mice that received DC1 in combination with anti-PD-1 antibody had superior efficacy in delayed tumor growth and improved survival rate. TUBO- bearing mice that received regimen-1, with DC1 vaccine and checkpoint antibodies concurrently had no significant delay in the tumor growth compared to mice treated with DC1 alone. Induction of anti-tumor immune response using HER2 specific MHC class II peptide- pulsed DC vaccine in combination with immune checkpoint blockade is ongoing. Overall, these findings suggest that optimal scheduling of immune checkpoint blockade is critical in improving anti-tumor efficacy of DC1 vaccine. This could be a potential combinatorial approach for the treatment of HER2 positive breast cancer in clinical settings. Citation Format: Krithika N. Kodumudi, Doris Wiener, Amrita Basu, Brian Czerniecki. Antitumor efficacy of Type I polarized dendritic cells in combination with immune checkpoint blockade in a preclinical model of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2545.