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Adoptive transfer of cytotoxic T cells(CTLs)that recognize and kill cancer cells is a promising cancer immunotherapy,and has been shown to achieve objective tumor regression in patients,such as patients with metastatic melanoma.However,this therapy is limited by the difficulty of obtaining sufficient numbers of tumor-reactive CTLs from cancer patients.Moreover,the lack of a clinically-relevant in vivo model remains a key bottleneck for the development of effective treatment protocols.Here we addressed these issues using innovative humanized mouse(hu-mouse)models.We have previously shown that transplantation of human thymus tissue and CD34+hematopoietic stem/progenitor cells in immunodeficient mice leads to the development of human lymphohematopoietic cells including T,B and dendritic cells,and the formation of secondary lymphoid organs consisting of human lymphohematopoietic cells.Recently,we developed a protocol for making human melanoma antigen MART1-specific TCR-transgenic(Tg)hu-mice,and demonstrated the feasibility of large scale production of MART1-specific human T cells in this model.Adoptive transfer of hu-mouse-derived MART1-specific human CD8 T cells induced potent antitumor responses in melanoma-bearing recipients.Furthermore,we successfully generated hu-mice with a functional human lymphohematopoetic system and autologous leukemia,providing an ideal clinically-relevant in vivo model for testing leukemia therapies.These findings highlight the potential of hu-mice as a preclinical model for translational cancer research.