Aim: The combination of tumor-targeting IL2 and TNF based antibody-cytokine fusions has exhibited encouraging results in mouse and men. Here, we studied their combination to assess efficacy and mechanism of action in four different immunocompetent mouse models of cancer. Methods: Mice receiving a single intratumoral injection of F8-IL2, F8-TNF or the combination were investigated for tumor-infiltrating leucocytes and rechallenged when cured. Results: In three models, a proportion of treated

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... als could be cured, most probably by infiltrating NK and CD8 + T cells. Most of the cured mice did not acquire protective immunity when rechallenged with the same tumor cell line. Conclusion: Immunocompetent mouse tumor models may not be adequate enough to predict the search for more efficacious therapy regimens. Précis A single intralesional injection of two tumor-targeting antibody-cytokine fusion proteins led to tumor eradication in three out of four different tumor models. However, cured mice did not develop protective immunity upon tumor rechallenge.