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Therapeutic testing in animal models has been the cornerstone of translational medicine. However, this trend is starting to change in favour of non-animal alternatives. Considering the high failure rates of forward translation from animal models to human application, the above paradigm shift is definitely welcome. But the enthusiasm toward this progress should not become the basis for completely replacing animal testing because the reliability and representativeness of non-animal alternatives still needs more investigation. And this particularly applies to analyses of the immune system and validation of immunotherapies. In this editorial, we discuss the application of reverse translation as a possible key to robustly connecting human immune data with animal testing to increase the benefit-to-risk ratio of translating immunotherapies toward prospective clinical trials.
