Analogous to the clinical use of recombinant high-affinity antibodies, transfer of T cell receptor genes may be used to create a T cell compartment specific for self-antigens to which the endogenous T cell repertoire is immune tolerant. Here we show in a spontaneous prostate carcinoma model that the combination of vaccination with adoptive transfer of small numbers of T cells that are genetically modified with a tumor-specific TCR results in a marked suppression of tumor development, even though both treatments are by themselves without effect. These results demonstrate the value of TCR gene transfer to target otherwise non-immunogenic tumor-associated self-antigens provided that adoptive transfer occurs under conditions that allow in vivo expansion of the TCR-modified T cells.