Abstract 5620: CD34+humanized huHSC-NCG mice engrafted with hematological malignancies models for preclinical study of anti-human CD19 therapeutic antibodies

Abstract

Abstract CD19, has become a vital immune and cellular therapeutic target to treat B-cell malignancies, as anti CD19 antibodies has produced remarkable clinical outcomes. Due to the lack of functional murine T cells, as well as B and NK cells, NCG mice engrafted with CDX or PDX models are well suited for evaluating CAR-T anti-tumor efficacy, but do not meet the needs of evaluating in vivo anti-tumor efficacy of anti-human CD19 bispecific or tri-specific antibodies that require functional human T cells.huHSC-NCG mice were established by the engraftment of CD34+ hematopoietic stem cells (HSC) into irradiated NCG mice. Among multi-lineages of human immune cells, the level of reconstituted human CD3+ T cells gradually increased in huHSC-NCG mice from 10 weeks after engraftment for long-term efficacy evaluation study. Both CD8+ cytotoxic and CD4+ helper T lymophocytes were detected by FACS in blood circulation. In this study, we established mice engrafted with Raji-Luciferase lymphoma and orthotopically engrafted with Nalm6-Luciferase leukemia cells. Both Blinatumomab and tri-specific antibodies displayed a pharmacological effect by reducing the proportion and total counts of B cells in circulation, showed significant tumor growth inhibition and prolonged the survival of xenograft huHSC-NCG mice. Taken together, huHSC-NCG mice is an ideal mouse model for preclinical study of bi-specific or tri-specific T cell engager therapeutic antibodies. Citation Format: Weiwei Yu, Cunxiang Ju, Hongyan Sun, Mingkun Zhang, Honghong Bao, Shuai Li, Chao Ju, Jing Zhao, Xiang Gao. CD34+humanized huHSC-NCG mice engrafted with hematological malignancies models for preclinical study of anti-human CD19 therapeutic antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5620.