Timing Of Pd-1 Blockade Is Critical To Successful Synergy With Ox40 Costimulation In Preclinical Mammary Tumor Models

With the recent success of cancer immunotherapies targeting specific inhibitory receptors like PD-1 and CTLA-4, there is great interest in how to combine these drugs with other novel therapies targeting costimulatory receptors that could further augment an anti-tumor response. Recently, we observed that orthotopically-transplanted MMTV-PyMT tumor-bearing mice that received anti-OX40 treatment saw a significant delay in tumor growth (p We hypothesized that treating with anti-PD-1 antibody would be more effective during the contraction phase of the T cell boost generated by anti-OX40. Thus we delayed anti-PD-1 treatment until after anti-OX40 dosing was complete and saw a significant delay (p Investigating the effects of the concurrent combination, we noticed a striking increase in IFN-γ in the serum compared to treatment with single agent (p Our results demonstrate that the sequence of antibody treatment targeting both costimulatory and inhibitory receptors is critical to success of the combined therapy. These data offer a strong rationale for delaying PD-1 blockade until after costimulation has provided an initial immune boost. Citation Format: David J. Messenheimer, Zipei Feng, Keith W. Wegmann, Shawn M. Jensen, Carlo B. Bifulco, Bernard A. Fox. Timing of PD-1 blockade is critical to successful synergy with OX40 costimulation in preclinical mammary tumor models. [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 4361.