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Characterization of a xenograft model for anti-CD19 CAR T cell studies

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Abstract

Purpose

Chimeric antigen receptor (CAR) T cell development for B cell malignancies treatment has triggered a paradigm shift in oncology. The development of anti-CD19 CAR T cells relies primarily on a panel of cell line-derived xenograft models, including Raji cells; however, the behavior of this model is under debate. We attempted to characterize this lymphoma model and propose outcome measures for CAR T cell studies

Methods

Raji cell line was inoculated into NOG mice via intra-venous (IV), intra-peritoneal (IP), and subcutaneous (SC) routes with different inoculum sizes, and consequent clinical and histopathological outcomes were assessed.

Results

Inoculum sizes of 105–106 resulted in a complete take rate. The mice with IV and SC-inoculated Raji cells presented the shortest and longest survival among lymphoma-bearing mice, respectively (P < 0.01). The IP group had the highest number of both infiltrated organs (P < 0.05; compared to SC) and involvement of lymphatic sites (P < 0.05; compared to IV). The number of lymphoma lesions on the liver was higher in the IV compared to IP (P < 0.001) and SC (P < 0.05).

Conclusion

We demonstrate that the Raji cell line inoculation route could determine the xenograft model system behavior in terms of survival, tumor burden, and dissemination pattern and gives the model the specific features suitable for testing the specific hypothesis in CAR T cell therapy. We also conclude outcome measures for CAR T cell studies that do not require imaging techniques.

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Data availability

Available on request.

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Funding

This research was supported by a research grant from Tehran University of Medical Sciences.

Author information

Authors and Affiliations

  1. Gene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    N. Ahmadbeigi, A. Ranjbar, S. Aghayan, A. Khorsand, K. Moradzadeh, M. Jamali & S. Muhammadnejad

  2. Digestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    S. Alatab

  3. Cell-Based Therapies Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    M. Vasei

  4. SABZ Biomedicals Science-Based Company, Tehran, Iran

    A. Ranjbar, S. Aghayan & K. Moradzadeh

  5. Flowcyt Science-Based Company, Tehran, Iran

    Z. Darvishyan

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  1. N. Ahmadbeigi
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Correspondence to S. Muhammadnejad.

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Animal experimentation was conducted under a protocol approved by the Ethical Committee of Tehran University of Medical Sciences.

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This work was a preclinical study. Therefore, informed consent was not applicable.

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Ahmadbeigi, N., Alatab, S., Vasei, M. et al. Characterization of a xenograft model for anti-CD19 CAR T cell studies. Clin Transl Oncol 23, 2181–2190 (2021). https://doi.org/10.1007/s12094-021-02626-5

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  • DOI: https://doi.org/10.1007/s12094-021-02626-5

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