Immune rejection in a humanized model of murine prostate cancer.

Background/aim: We attempted to develop a humanized mouse model for prostate cancer to study immune recognition and responses to human prostate-tumor antigens in mice.

Materials And Methods: Our study was based on cell lines derived from transgenic adenocarcinoma of the mouse prostate (TRAMP) tumors. TRAMP cells were modified to express a chimeric MHC I molecule comprising the extracellular domains of human HLA-A2.1 with the transmembrane and intracellular domain of K(b).

Results: These modified TRAMP cells were immunologically rejected following recognition of human tumor epitopes known to be immunodominant in the context of HLA-A2.1. Immune-compromised SCID-beige mice did not reject these tumors.

Conclusion: We conclude that epitopes derived from endogenous murine homologs were being presented by the chimeric MHC class I molecules due to a lack of central tolerance to these epitopes in the mice.