Abstract

Abstract Currently more and more immunotherapeutic drugs and engineered cells have been developed to use human immune system against cancer. While humanized peripheral blood mononuclear cell reconstitution in immune deficient mice is a forward-straight model for evaluating therapeutic antibodies, this conventional model has several drawbacks to hinder its widespread use, including the graft-versus-host-disease happened after one month of reconstitution, insufficient immune cell infiltration from reconstituted circulatory system and hardly retention of functional innate immune cells, such as macrophages and nature killer cells. To overcome this, LIDE has developed a specific human immune cell and cancer cell co-inoculation model. Cancer-priming PBMC and/or its derivates were well mixed with the fresh cancer cells in MatriGel, co-transferring into NCG mice to form a relatively “hot tumor” tissue for immunotherapy, including drugs targeting T cells, dendritic cells and macrophages. Additionally, we also take advantage of human IL15 transgenic mice to study the function of ex vivo expanded NK cells. This novel method has successfully helped evaluate biological function of immune checkpoint blockers and immune agonists in multiple cancers, such as melanoma, breast cancer, lung cancer, hepatocellular carcinoma and ovarian cancer. Citation Format: Bin Xie, Xin Hou, Hanglu Chen, Pengfei Yang, Yanbin Zhou, Danyi Wen. Novel Immuno-Oncology drugs evaluation by humanised immune cells and cancer co-inoculated models. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5200.

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