Abstract
Abstract Backgrounds: Despite the unprecedented success of immune checkpoint antibody therapy in patients with various cancer types, lack of stable experimental immunotherapy models is still a big challenge in development of effective new immune-therapeutics. Different strategies of humanized mouse model system, including human hematopoietic stem cell (HSC) or human PBMC humanization in immune-deficient mice, or chimeric models harboring human immune checkpoint targets in immune-competent mice have been reported. CrownBio has successfully established a number of human PBMC-humanized xenograft models MiXenoTM for in vivo IO therapy evaluation, which has been shown to be a rapid and simple strategy of humanization. However, several outstanding questions, e.g. the optimal PBMC injection route and cell number, the donor dependence of the efficacy result and impact of donor HLA type on the efficacy, etc., need to be further addressed. Results: PBMC number was titrated in one of our MiXenoTM model HCC827, and PBMC injection via i.p. vs. i.v. was compared. Tumor growth curve, graft versus host disease (GVHD), and blood immunophenotyping were followed under different settings. Furthermore, the antitumor activity of PD-1 antibody pembrolizumab in a panel of PBMC donor context that bears diversified HLA types was precisely analyzed. We found that the efficacy was highly donor dependent, and there was lack of correlation between efficacy and donor/tumor HLA match. Conclusion: The MiXenoTM model provides an alternative to the full stem cell reconstitution approach. Better understanding on the characteristics of the model may allow a rational model selection and study design in the discovery IO therapeutics. Citation Format: Juan Zhang, Qian Shi, Lan Zhang. Characterization of MiXenoTM humanized mouse model for immuno-oncological therapy evaluation [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 1647. doi:10.1158/1538-7445.AM2017-1647
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