Abstract AP28: ANTITUMOR RESPONSE AFTER VACCINATION TARGETING INSULIN GROWTH FACTOR BINDING PROTEIN 2 IN A SYNGENEIC MOUSE MODEL OF OVARIAN CANCER LOCALIZED BY THREE-DIMENSIONAL IN VIVO OPTICAL IMAGING
Authors: Denise L. Cecil, Neal Paragas, Katie M. Hitchcock-Bernhardt, Mary L. Disis, John B. Liao
Journal: Clinical Cancer Research (2019)

Abstract INTRODUCTION: Ovarian cancer often disseminates as miliary implants throughout the peritoneal cavity presenting challenges for tumor quantitation in both the clinical and pre-clinical settings. The distribution of tumor implants shows affinity for areas such as the omentum and lymph nodes, which may be included in a cytoreductive surgery. Immunotherapies are being studied for ovarian cancer due to the high rate of relapse and resistance to available treatments in the recurrent setting. Pre-clinical models for ovarian cancer often do not allow meaningful assessment of novel immune-based therapies. We hypothesized vaccination targeting insulin growth factor binding protein 2 (IGFBP-2) will result in antitumor responses that can be both quantitated and localized spatially with optical imaging to identify tumor implants most resistant to vaccination. METHODS: C57BL/6/BrdCrHsd-Tyrc mice received 4 immunizations with IGFBP-2 peptides corresponding to epitopes known to favor antitumor immunity with Freund's adjuvant (treated) or with adjuvant alone (control). 5 x 106 cells of a syngeneic mouse model expressing codon-optimized firefly luciferase (luc2) known to replicate the immune microenvironment of human ovarian cancers were injected intraperitoneally. After two weeks mice were anesthetized prior to injection of D-luciferin and during imaging via inhalation of isoflurane. Mice were placed in conforming animal molds (BCAM: InVivo Analytics, Inc.) and multi-view multi-spectral image acquired with the InVivoPLOT mirror-gantry. Bioluminescent tomographic (BLt) images were reconstructed using InVivoAX (InVivo Analytics, Inc.) cloud-based software and aligned to the organ probability map (OPM), a type of statistical mouse atlas. RESULTS: Surface light intensity showed a 5.41 x 109 photons/second/mouse in control compared to 1.32 x 109 photons/second/mouse in IGFBP-2 vaccinated when measured in two dimensions. Multi-spectral tomographic reconstruction was able to show a greater than 2-fold decrease in the spatial light distribution of bioluminescent metastasis consistent with the surface light intensity distribution of the BLt image. BLt images mapped to the OPM discriminate the miliary distribution of metastases in the peritoneum. Individual metastasis in the control were shown to have a greater relative light density than the individual metastasis in the IGFBP-2 vaccinated group. CONCLUSIONS: In vivo anatomic localization of antitumor activity in a disseminated ovarian cancer mouse model can be achieved using three-dimensional optical imaging. Local differences in antitumor response to immunotherapies may be exploited to optimize their application to ovarian cancer. Identifying where tumor implants resistant to immunotherapies are sequestered may improve pre-clinical testing of immunotherapy combinations and optimally integrate them into current standard therapies. Citation Format: Denise L. Cecil, Neal Paragas, Katie M. Hitchcock-Bernhardt, Mary L. Disis, John B. Liao. ANTITUMOR RESPONSE AFTER VACCINATION TARGETING INSULIN GROWTH FACTOR BINDING PROTEIN 2 IN A SYNGENEIC MOUSE MODEL OF OVARIAN CANCER LOCALIZED BY THREE-DIMENSIONAL IN VIVO OPTICAL IMAGING [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr AP28.