Development of Advanced Human Immune System Mouse Models for Pre-Clinical Research in Immuno-oncology

Abstract

Abstract Background The reconstitution of a fully functional human immune system in the NCG mouse (hu-NCG) provides a unique opportunity to assess the efficacy of new drug candidates acting on human immune cells such as T cells, myeloid cells and NK cells. Enhanced NCG mice have been further developed to boost the differentiation of myeloid and NK cells, allowing scientists to efficiently test new antibodies or small molecules targeting these immune cell populations. Methods A fully functional human immune system has been reconstituted in NCG mice after the transplantation of CD34+ human stem cells (hu-NCG model). Then, cell-line derived xenografts (CDX) and patient derived xenografts (PDX) have been engrafted in the hu-NCG model. The tumor growth has been monitored and the immune response assessed by flow cytometry. Results We observed infiltration of human immune cells in the tumors. Furthermore, checkpoint inhibitors such as anti-PD1 strongly reduced tumor growth in hu-NCG demonstrating the potency of this model in onco-immunology. Alternatively, we demonstrated that hu-NCG, immunized against cancer antigens elicits strong T cell response as well as IgG production. Conclusion Collectively, the huNCG mouse model demonstrats its relevance for the preclinical testing (Mono and Combo therapies) of drugs in immuno-oncology. Legal entity responsible for the study The authors. Funding Transcure Bioservices. Disclosure All authors have declared no conflicts of interest.