Abstract 2668: Efficacy study of immuno-checkpoint antibodies in humanized CDX and PDX models

Abstract

Abstract Immune therapeutic intervention has been accepted widely for many hematopoietic malignancies and solid malignancies in past several years. Preclinical animal models with reconstitution of immune cells and target-expressing tumor cells were urgently needed for prove of concept studies demonstrating stimulatory immune system activation. Here we describe two established models of human PBMC co-transplantation of CDX and PDX. The study design was based on co-inoculation of human PBMC and PD-L1 expressing cell in NOG mice for reconstitution of immuno-checkpoint blockage. A therapeutic anti-PD1 antibody was applied for immune system activation and tumor growth inhibition measurement. After drugs were administrated i.p. for three weeks, 95 % TGI for A375 CDX model were observed. At the termination of the efficacy study at 28 days post therapeutic intervention, tumors of vehicle (tumor only, PMBC only), PD1 Ab treated groups were collected for immunostaining of CD45. Infiltrating T-cell with CD45+ label was found within the tumors when co-inoculated with human PBMC. PBMC humanized PDX models of ovarian cancer was implanted into mice which reconstituted with human PBMC for therapeutic intervention. Results showed that 85% TGI for PBMC humanized ovarian PDX models was observed. In conclusion, the models established here are feasible for immunotherapeutic evaluation and further additional immune therapeutic test articles can be explored with similar approaches. Citation Format: Feifei Zhang, Yang Yang, Hongkui Chen, Lijun Jia, Kedong Ouyang, Danyi Wen, Taiping Chen. Efficacy study of immuno-checkpoint antibodies in humanized CDX and PDX models [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 2668. doi:10.1158/1538-7445.AM2017-2668