The Confounding Role of Graft-Versus-Host Disease in Animal Models of Cancer Immunotherapy: A Systematic Review

TL;DR

This paper reviews how graft-versus-host disease affects cancer immunotherapy studies in animals and suggests ways to improve preclinical research accuracy.

Contribution

The paper systematically reviews strategies to mitigate GVHD confounding in animal models of cancer immunotherapy.

Findings

Genetically modified mouse models and immunosuppressive drugs are used to mitigate GVHD effects.

Selective T-cell depletion and cytokine inhibitors are innovative approaches identified in the review.

Mitigating GVHD improves preclinical trial validity and translational outcomes in cancer immunotherapy.

Abstract

Cancer immunotherapy has emerged as a transformative approach for treating various malignancies, including melanoma, lung cancer, breast cancer, and leukemia. Animal models have been instrumental in elucidating the mechanisms and potential of these therapies. However, graft-versus-host disease (GVHD) is an inherent challenge in these studies, primarily because the introduction of foreign immune cells or tissues often triggers immune responses.

A detailed systematic search was conducted across various scientific databases, including PubMed, Scopus, Embase, and Web of Science. The search aimed to identify peer-reviewed articles published in English from January 2000 to September 2023. Keywords and phrases used in the search included "Graft-versus-Host Disease", "GVHD", "animal models", "cancer immunotherapy", and combinations thereof. Boolean operators (AND/OR) were employed to refine the search. Finally, 6 articles were included in this systematic review, which is registered on PROSPERO (ID number CRD42024488544).

Our systematic review identified several mechanisms employed in animal studies to mitigate the confounding effects of GVHD. These included genetically modified mouse models, immunosuppressive drugs, and humanized mice. Furthermore, the review highlights innovative approaches such as selective T-cell depletion and the use of specific cytokine inhibitors.

By systematically identifying and mitigating the confounding effects of GVHD, we can significantly improve the predictive validity of preclinical trials, obtain broadly applicable findings, improve the efficiency of drugs, enhance safety profiling, and develop better therapeutic strategies. This approach is crucial in ensuring that the immunotherapeutic strategies developed in the laboratory are reflective of the human physiological response, thereby bridging a critical translational gap in oncological research.

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