CD147-CAR-NK Cell Therapy Shows Minimal Toxicities in Human CD147 Transgenic Mouse Model with Solid Tumors — ASN Events
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  2. Lightning Session One
  3. CD147-CAR-NK Cell Therapy Shows Minimal Toxicities in Human CD147 Transgenic Mouse Model with Solid Tumors

CD147-CAR-NK Cell Therapy Shows Minimal Toxicities in Human CD147 Transgenic Mouse Model with Solid Tumors (#172)

Youssef YS Sabha 1 , Sang Hoon SK Kim 1 2 , Sang Hoon SL Lee 1 2 , Hsiang-chi HT Tseng 1 , Bryan BT Tsao 1 , Maeve MB Byrne 1 , Mi-hyeon MJ Jang 2 , Dongfang Liu 1
  1. Rutgers University, Newark, NJ, United States
  2. Department of Neurosurgery, Robert Wood Johnson Medical School, Piscataway, NJ, USA

The neurotoxicity of CAR-NK has not been tested in solid tumor, compared with CAR-T therapy side-by-side. To address this, we investigated the CD147-CAR-NK “on-target & off-tumor” toxicity and neurotoxicity in humanized CD147-transgenic (hCD147TG) mice with hepatocellular carcinoma. We first tested in vitro cytotoxicity of CD147-CAR-NK against CD147+ tumor and CD147+ healthy cells. Both CD147-CAR-NK cells and CD147-IL15-CAR-NK (autocrine expressing IL-15) can kill tumor cells specifically, but not CD147+ healthy lung and spleen tissue from hCD147TG mice. In vivo assays show minimal systemic toxicities against CD147+ healthy tissues, but one-week longer persistence time in tumor than non-tumor tissues. To evaluate neurotoxicity, we compared the expression of IBA1, GFAP, and iNOS between CD147-CAR-T and CD147-CAR-NK-treated hCD147TG mice with HCC. Both CD147-CAR-T and CD147-CAR-NK treated mice exhibited higher GFAP and IBA1 expression than control groups. CD147-CAR-T treated mice show an increase on iNOS, compared to control groups. The behavioral studies testing spatial memory showed that mice treated with CD147-CAR-NK exhibit better memory function than CD147-CAR-T-treated mice. This study provides a deeper understanding of the CD147-CAR-NK systemic toxicities and neurotoxicity of CD147-CAR-NK relative to CD147-CAR-T therapy.