Recent investigations revealed strong immunosuppressive mechanisms in tumors that may block anti-tumor T cells and be responsible for failures of immunotherapies. Current attempts to overcome this immunosuppression include blockade of co-inhibitory factors on T cells. Reports from the respective trials indicate that the strategy can improve efficacy of therapeutic vaccination, but at the cost of severe inflammatory and autoimmune reactions. We tried to circumvent tumor-associated immunosuppression by mimotope vaccination to broaden reactive anti-tumor T cell repertoires to include T cells that have not been rendered anergic by the tumor. Initial clinical observations suggest that this strategy bears considerable promise.