New York Academy of Sciences’ Frontiers in Cancer Immunotherapy – Unique Immunodeficient Murine Host Strains Impact Expansion and Engraftment of T Cells in PBMC Humanized Mice

Title:

Unique Immunodeficient Murine Host Strains Impact Expansion and Engraftment of T Cells in PBMC Humanized Mice

Authors:

Bhavna Verma, Bruce Ruggeri, Philip E. Dube, Mark Volden, Amy Wesa

Abstract:

The development of animal models capable of mimicking human immune responses and functions are crucial to study the safety and efficacy of immune checkpoint inhibitors, functionality of CAR-T therapies, and immuno-oncology treatments including gene and cell therapies. Mice reconstituted with human hematopoietic stem cells (HSC) are able to differentiate and repopulate human immune cells sufficient to model many aspects of tumor immunity. In partnership with the Central Institute for Experimental Animals (CIEA), Taconic Biosciences has developed the CIEA NOG mouse® (NOG) portfolio which is a powerful tool, capable of accepting human HSC that develop into multiple immune cells including T cells. The NOG mouse is the ideal host for human tumor xenografts due to its hyper-immune deficiency caused by the IL-2Rg mutation and NOD/scid background Taconic and the CIEA have continued to expand the NOG portfolio with a variety of next-generation immune-deficient NOG mice that are suitable and highly effective at modeling the diverse mechanistic functions of human immunity as well as being the host for human tumor xenografts including patient-derived xenografts, (PDX). This presentation will focus on the current state of human immune system engraftment models (huNOG and huNOG-EXL) and the utilization of the wide range of the NOG mouse portfolio, as the next generation model that diversifies the mechanistic functionality of immune engraftments and recent advances in modeling human immunity in immuno-oncology applications.