Background: Fighting cancer by taking advantage of a patient's own immune system is showing considerable success in oncology research. Targeting therapeutic antibodies against tumor-associated antigens or the host immune system has been shown to prolong survival of patients in various tumor types. However, the lack of experimental immunotherapy models is a major obstacle toward better evaluating new immunotherapeutics and testing their exploratory combination strategies. To address this need, we set out to validate a new platform MiXenoTM by implanting human PBMC to immune-deficient mice. The MiXenoTM mice were partially reconstituted with human immune components. In vivo efficacy of several immunotherapeutics were evaluated.
Results: We have reported before that several MiXenoTM models could be used to evaluate anti-human PD-1 or PD-L1 antibodies, where human T cells were well reconstituted in the mouse system. Here one of our MiXenoTM collection: HCC827 model was further optimized and identified as a PD-1/PD-L1 inhibitor highly sensitive model. Involvement of T cells in the tumor microenvironment was observed in HCC827 tumors. Furthermore, the dynamics of NK cell population in blood, tumor and other organs (e.g. spleen and lymph nodes) was established in MiXenoTM models. NK cell function was evaluated as well.
Conclusion: The MiXenoTM model provides an alternative to the full stem cell reconstitution approach, and may allow various types of immunotherapies being evaluated in these partially humanized xenograft models.
Citation Format: Juan Zhang, Meng Qiao, Jian Ding, Zhensheng Wang, zhongliang Li, Qian Shi. MiXeno Humanized Mouse Model as an Efficient Tool to Evaluate in Vivo Activity of Anti-Cancer Immunotherapeutics. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5184.