Combination of rapamycin with immune checkpoint blockade in a syngeneic breast carcinoma model

AACR Annual Meeting 2018

Poster: Combination of Rapamycin with Immune Checkpoint Blockade in a Syngeneic Breast Carcinoma Model

Introduction and Background

Many advances in the treatment of breast cancer have been driven by the development of targeted therapies that inhibit signal transduction pathways, as well as the development of therapies that activate a patient’s immune system to unleash antitumor immunity. The choice of an animal model that mimic aspects of human breast cancer is crucial for evaluating new immunotherapeutic combination strategies. An excellent syngeneic model of breast cancer is 4T1. 4T1-luc2 is poorly immunogenic and shares many characteristics with human breast cancer. To understand the potential benefit from combining a targeted therapy with an immune modulator we utilized the orthotopic 4T1-luc2 model. The mTOR pathway plays an important role in metabolism, cell growth and survival. Targeting mTOR has been an active area of oncology drug discovery and clinical development for breast cancer and other malignancies. In addition, clinical success through blockade of the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) has resulted in a paradigm shift for drug development within the oncology community. To this end, we designed a series of experiments to evaluate rapamycin, a first generation mTOR inhibitor, in combination with the immune checkpoint inhibitor antibody against CTLA-4.