Human CD22-transgenic, primary murine lymphoma challenges immunotherapies in organ-specific tumor microenvironments

Gsottberger F, Brandl C, Wendland K, Petkovic S, Emmerich C, Erber R, Geppert CI, Hartmann A, Mackensen A, Nitschke L, Müller F (2021)


Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 22

Article Number: 10433

Journal Issue: 19

DOI: 10.3390/ijms221910433

Abstract

Targeted immunotherapies have greatly changed treatment of patients with B cell malignancies. To further enhance immunotherapies, research increasingly focuses on the tumor microenvironment (TME), which differs considerably by organ site. However, immunocompetent mouse models of disease to study immunotherapies targeting human molecules within organ-specific TME are surprisingly rare. We developed a myc-driven, primary murine lymphoma model expressing a human-mouse chimeric CD22 (h/mCD22). Stable engraftment of three distinct h/mCD22+ lymphoma was established after subcutaneous and systemic injection. However, only systemic lymphoma showed immune infiltration that reflected human disease. In this model, myeloid cells supported lymphoma growth and showed a phenotype of myeloid-derived suppressor cells. The human CD22-targeted immunotoxin Moxetumomab was highly active against h/mCD22+ lymphoma and similarly reduced infiltration of bone marrow and spleen of all three models up to 90-fold while efficacy against lymphoma in lymph nodes varied substantially, highlighting relevance of organ-specific TME. As in human aggressive lymphoma, anti-PD-L1 as monotherapy was not efficient. However, anti-PD-L1 enhanced efficacy of Moxetumomab suggesting potential for future clinical application. The novel model system of h/mCD22+ lymphoma provides a unique platform to test targeted immunotherapies and may be amenable for other human B cell targets such as CD19 and CD20.

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How to cite

APA:

Gsottberger, F., Brandl, C., Wendland, K., Petkovic, S., Emmerich, C., Erber, R.,... Müller, F. (2021). Human CD22-transgenic, primary murine lymphoma challenges immunotherapies in organ-specific tumor microenvironments. International Journal of Molecular Sciences, 22(19). https://dx.doi.org/10.3390/ijms221910433

MLA:

Gsottberger, Franziska, et al. "Human CD22-transgenic, primary murine lymphoma challenges immunotherapies in organ-specific tumor microenvironments." International Journal of Molecular Sciences 22.19 (2021).

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