Abstract 1584: Efficacy and pharmacodynamic effect of anti-CD73/PD-L1 monoclonal antibodies in combination with chemotherapy: Observations from mouse tumor models

Intratumoral adenosine is a key immunosuppressive factor linked to poor prognosis and reduced efficacy of T cell checkpoint inhibitors. CD73 is an ectoenzyme and key node in the catabolic pathway responsible for sequential hydrolysis of extracellular ATP to adenosine. ATP is released from necrotic and damaged tumor cells; a phenomenon enhanced as consequence of cytotoxic chemotherapy or radiotherapy. A CD73 inhibiting human monoclonal IgG1-TM antibody, Oleclumab, is currently in phase 2 clinical development for treatment of patients with various solid tumors. The combination of CD73 inhibition with chemotherapy and T cell checkpoint inhibition was tested using two murine cancer models, CT26 (colorectal) or MCA205 (fibrosarcoma) implanted subcutaneously in BALB/c mice or C57BL/6 mice, respectively. Tumor bearing mice were treated with combinations of oxaliplatin and 5-fluorouracil and murine surrogate monoclonal antibodies for Oleclumab and Durvalumab (anti-PD-L1). CT26 implanted mice were also treated with the murine surrogate antibodies in the presence and absence of Docetaxel. In an attempt to define contribution of components, comparator groups received monotherapies and other iterations of the combination. Treatment with anti-CD73 and anti-PD-L1 antibodies, concomitantly with chemotherapy, resulted in improved tumor growth inhibition, plus increased proportions of complete tumor regression (P