EP208/#677 Combination of IGF1R inhibition with PD-1 blockade results in significant anti-tumoral activity in epithelial ovarian cancer

Objectives

The insulin-like growth factor (IGF) system plays a key role in regulating growth and invasiveness in epithelial ovarian cancer (EOC), therefore, is regarded as a promising therapeutic target. Recently, it has been shown that the IGF1 axis can regulate dendritic cells (DC) maturation and T cell activation. Our study aims to investigate the combination effect of IGF1 receptor (IGF1R) inhibition along with anti-PD-1 on EOC. We believe that this combination may reverse immune escape in EOC patients.

Methods

EOC cell lines were co-cultured with IGF1R inhibitor (AEW-541)-treated-DCs. DC differentiation and EOC proliferation levels were evaluated by Flow Cytometry Assay (FACS). C57BL/6 mice with established peritoneal ID8 OC were injected with single or combined anti-PD-1 and AEW-541, and their survival was evaluated. Myeloid DCs and T-cell population levels were analyzed by FACS. Finally, RNA from tumors was extracted and submitted for RNAseq analysis (results are pending).

Results

IGF1R inhibitor treatment induced DC differentiation. In addition, (AEW-541)-treated-DCs significantly decreased EOC cell proliferation. Combined anti-PD-1/IGF1R treatment decreased tumor weight compared to single treatments. Moreover, the anti-PD-1/IGF1R treatment significantly increased the Myeloid DC1 frequencies by 34% and 40%, and DC2 frequencies by 10% and 24% compared to AEW-541 and anti-PD-1 treatments, respectively. Additionally, the combined treatment increased CD8+ T-cells levels (115%) compared to AEW-541 treatment.

Conclusions

IGF1R pathway inhibition in differentiated DCs suppressed EOC cell proliferation. IGF1R inhibitor combined with anti-PD-1 may result in enhanced anti-tumor activity. Thus, restoring the anti-tumor immune response by IGF1R targeting in combination with immunotherapy may be an effective therapy for EOC.