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Potential lung attack and lethality generated by EpCAM-specific CAR-T cells in immunocompetent mouse models.

Publication ,  Journal Article
Qin, D; Li, D; Zhang, B; Chen, Y; Liao, X; Li, X; Alexander, PB; Wang, Y; Li, Q-J
Published in: Oncoimmunology
August 15, 2020

The tumoricidal efficiency of human CAR-T cells is generally evaluated using immune-deficient mouse models; however, due to their immune-incompetency and the species-specific reactivity of a target antigen, these models are problematic to imitate CAR-T-induced adverse effects in the clinic. Epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen overtly presented on the cell surface of various carcinomas, making it an attractive target for CAR-T therapy. Here, we developed an anti-mouse EpCAM CAR to evaluate its safety and efficacy in immunocompetent mouse models. As previously reported for their human equivalents, murine EpCAM CAR-T cells exhibit promising anti-tumor efficacy in vitro and in vivo. However, after CAR-T infusion, various dose-depended toxicities including body weight loss, cytokine-release syndrome (CRS), and death were observed in both tumor-bearing and tumor-free mice. Pathological examination revealed unexpected and severe pulmonary immunopathology due to basal EpCAM expression in normal lung. While our study validates EpCAM CAR-T's potent anti-tumor efficacy, it also reveals that EpCAM CAR-T cells used for the treatment of solid tumors may cause lethal toxicity and should, therefore, be evaluated in patients with caution.

Duke Scholars

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Published In

Oncoimmunology

DOI

ISSN

2162-4011

Publication Date

August 15, 2020

Volume

9

Issue

1

Start / End Page

1806009

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Receptors, Chimeric Antigen
  • Mice
  • Lung
  • Immunotherapy, Adoptive
  • Humans
  • Epithelial Cell Adhesion Molecule
  • Animals
  • 3211 Oncology and carcinogenesis
  • 3204 Immunology
 

Citation

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Qin, D., Li, D., Zhang, B., Chen, Y., Liao, X., Li, X., … Li, Q.-J. (2020). Potential lung attack and lethality generated by EpCAM-specific CAR-T cells in immunocompetent mouse models. Oncoimmunology, 9(1), 1806009. https://doi.org/10.1080/2162402X.2020.1806009
Qin, Diyuan, Dan Li, Benxia Zhang, Yue Chen, Xuelian Liao, Xiaoyu Li, Peter B. Alexander, Yongsheng Wang, and Qi-Jing Li. “Potential lung attack and lethality generated by EpCAM-specific CAR-T cells in immunocompetent mouse models.Oncoimmunology 9, no. 1 (August 15, 2020): 1806009. https://doi.org/10.1080/2162402X.2020.1806009.
Qin D, Li D, Zhang B, Chen Y, Liao X, Li X, et al. Potential lung attack and lethality generated by EpCAM-specific CAR-T cells in immunocompetent mouse models. Oncoimmunology. 2020 Aug 15;9(1):1806009.
Qin, Diyuan, et al. “Potential lung attack and lethality generated by EpCAM-specific CAR-T cells in immunocompetent mouse models.Oncoimmunology, vol. 9, no. 1, Aug. 2020, p. 1806009. Pubmed, doi:10.1080/2162402X.2020.1806009.
Qin D, Li D, Zhang B, Chen Y, Liao X, Li X, Alexander PB, Wang Y, Li Q-J. Potential lung attack and lethality generated by EpCAM-specific CAR-T cells in immunocompetent mouse models. Oncoimmunology. 2020 Aug 15;9(1):1806009.

Published In

Oncoimmunology

DOI

ISSN

2162-4011

Publication Date

August 15, 2020

Volume

9

Issue

1

Start / End Page

1806009

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Receptors, Chimeric Antigen
  • Mice
  • Lung
  • Immunotherapy, Adoptive
  • Humans
  • Epithelial Cell Adhesion Molecule
  • Animals
  • 3211 Oncology and carcinogenesis
  • 3204 Immunology