Most current cancer treatment strategies involve the use of chemotherapeutic or biological drugs that exhibit variable efficacy and considerable toxicity. The limitations are often the result of the adverse side effects of the therapeutic drug on normal tissues. One approach to control these effects is to target the therapy to the tumor site. Of the identified tumor antigens, the human p53 tumor suppressor protein is overexpressed in a wide range of human malignancies. p53 is an intracellular tumor suppressor protein that acts to arrest the proliferation of cells. When mutated, it loses its ability to suppress abnormal proliferation and exhibits a longer half-life than the wild-type protein, allowing for its accumulation in tumors. In addition, p53 overexpression correlates with tumor transformation and aggression and is associated with lower overall survival rates and resistance to chemotherapeutic intervention in cancer patients. Therefore, p53 appears to be a marker for a considerable number of human malignancies and represents a good target for immunotherapeutics. However, p53 cannot be used as a target for antibodies because it is not displayed independently on the cell surface. Instead, the p53 protein is processed intracellularly into peptide fragments that are then displayed on the cell surface in the context of major histocompatibility complex (MHC). These peptide/MHC complexes are recognized by T-cells via their T-cell receptors (TCRs). Recently it has been confirmed that the peptide fragment is significantly elevated in a wide range of human tumor tissues, particularly in melanoma, renal, lung, breast, colorectal, bladder, ovary, stomach, esophagus, lymphoma, liver, leukemia, and head & neck cancer. Targeted approaches to concentrate therapeutic cytokines at the tumor sites that express p53 could provide considerable advantages over current treatment.