LAUSR

Purpose: An intraoperative technique to accurately identify microscopic tumor residuals could be applied to decrease the risk of positive surgical margins. Several lines of evidence support the expression and immunotherapeutic effect of PD-1 in breast cancer. Here, we sought to develop a fluorescence labeled PD-1 probe for in vivo breast tumor imaging and image-guided surgery. The efficacy of PD-1 monoclonal antibody (mAb) as adjuvant immunotherapy after surgery was also assessed. Experimental Design: A near-infrared dye labeled PD-1-IRDye800CW probe was developed and examined for its application in tumor imaging and image-guided tumor resection in an immunocompetent 4T1 mammary mouse tumor model that recapitulates clinical metastatic cancer. Fluorescence molecular imaging (FMI) was performed to monitor probe biodistribution and intraoperative imaging. Bioluminescence imaging (BLI) was carried out concurrently to monitor tumor growth and evaluate post-surgical tumor residuals, recurrences, and metastases. Results: The PD-1-IRDye800CW probe exhibited a specific and stable signal at the tumor region compared to the IgG control, and exhibited the highest tumor-to-background ratio (TBR) 8 h post-injection (11.62 ± 0.79), approximately 5 fold higher than the IgG control (2.13 ± 0.30). Furthermore, PD-1-IRDye800CW guided surgery combined with PD-1 adjuvant immunotherapy inhibited tumor regrowth and microtumor metastases, as determined by BLI imaging, and thus improved survival rate with no obvious side effects. Conclusions: Our study demonstrated the feasibility of using PD-1-IRDye800CW for breast tumor imaging and image-guided tumor resection. Moreover, we found that PD-1 mAb adjuvant immunotherapy reduces cancer recurrences and metastases emanating from minimal tumor residuals. Citation Format: Yang Du, Jie Tian. Improved resection and prolonged overall survival with PD-1-IRDye800CW fluorescent probe-guided surgery and PD-1 adjuvant immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 875. doi:10.1158/1538-7445.AM2017-875