Abstract 2224: Discovery, development and characterization of a new class of therapeutic anti-PD-1 antibody

Blockade of immune checkpoint (IC), such as PD-1, confers durable clinical benefit to a minority of melanoma and lung cancer patients. Challengingly, the 5-year survival rate is still below 30% in those patients, and most other solid tumors are not particularly responsive to immunotherapy. Therefore, more IC blocking mAbs are under development to meet clinical needs. Using Enumeral9s unique single cell immunoprofiling platform, we developed a novel class of anti-PD-1 antibodies, named 244C8, with distinct epitope binding site than currently marketed anti-PD-1 antibodies. To evaluate the function of 244C8 on anti-tumor immunity, we employed ex vivo methods to determine responsiveness of tumor infiltrating lymphocytes (TILs), isolated from human lung cancer biopsies, to various anti-PD-1 antibodies, including our lead anti-PD1 therapeutic candidate 244C8. The results show that all anti-PD-1 antibodies tested reversed T cell exhaustion in tumor microenvironment. Further, 244C8-treated cells produced increased IFN-y compared to nivolumab, indicating a stronger anti-tumor immunity. In the settings of mixed lymphocyte reaction (MLR) and CMV antigen-recall assays, 244C8 treatment also led to higher levels of T cell activation compared to conventional anti-PD-1 antibodies. Interestingly, in both ex vivo and in vitro models, we observed a pattern of cytokine production in 244C8-treated cells that is consistently distinct from that produced by conventional/marketed anti-PD-1 antibodies, suggesting a differentiated mechanism of action. Citation Format: Lei Wang, Najmia Amirina, Fellix Scheuplein, Vikki Spaulding, Yanyan Wang, Sri Vadde, M. Isabel Chiu, Daniel Doty, Thomas McQuade, Bin Feng, Sheila Ranganath, Anhco “Cokey” Nguyen. Discovery, development and characterization of a new class of therapeutic anti-PD-1 antibody. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2224.