Evaluation Of Car-T Anti-Tumor Response In A Novel Immunocompromised Nod-Prkdc(Em26cd52)Il2rgem(26cd22)/Njucrl Mouse Model.

Abstract Background: The development of immunocompromised mice revolutionized the field of cancer and stem cell research. Due to the lack of mature B and T lymphocytes, SCID (severe combined immunodeficiency disease) mice are ideal for xenoengraftment of human cells and tissue, including patient-derived tumor cells, hematopoietic stem cells and T cells. Over the years, the SCID models have been implemented to increase the efficiency of engraftment and NSG (NOD-SCID;IL2Rgammanull) has become the most reliable in vivo human cancer model. Here we compared NSG with the novel mouse strain NCG for immune-oncology applications, in particular for CAR-T therapy. NCG (NOD-Prkdcem26Cd52Il2rgem26Cd22/NjuCrl) is a recently developed triple immunodeficient mouse strain, created by sequential CRISPR/Cas9 editing of the PRKDC and IL2rg loci in the NOD/Nju strain. For this purpose, we engrafted NALM-6 and CHLA-55 tumor cell lines and treated them with CD19 and GD2.CAR T cells, respectively. Results: Four different operators generally considered NCG mice to be easier to handle. NCG mice were a bit smaller and have a much smaller spleen compared to age-matched NSG mice. Tumor engraftment was particularly rapid in NCG while the dissemination to organs was comparable. Generally, NCG showed signs of sickness earlier and upon lower tumor burden. When treated with CAR-T cells, in vivo anti-tumor response was comparable, both in a leukemia mouse model (96.6% NSG vs 97.7% NCG) and in a disseminated neuroblastoma model (67.3% NSG vs 57.8% NCG).Conclusion: Our preliminary data show that NCG mice are a suitable immunocompromised host for CAR-T pre-clinical studies. Citation Format: Rashmi Bankoti, Amit Joshi, Lasse Jorgensen, Andreas Kongsgaard, Maddalena Adorno, Benedetta Nicolis di Robilant. Evaluation of CAR-T anti-tumor response in a novel immunocompromised NOD-Prkdcem26Cd52Il2rgem26Cd22/NjuCrl mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB166.