Stimulation of T cells to respond to self antigens is achieved through a blockade of CTLA-4 signaling. CTLA-4 blocking agents are combined with antigen preparations, either alone or with additional immune response stimulating agents, in costimulation strategies to break immune tolerance and stimulate an enhanced T-cell response against self antigens. This enhanced response is useful for the treatment of non-immunogenic and poorly-immunogenic tumors, as well as other medical conditions requiring selective tissue ablation.