ABSTRACT
Active immunotherapy harnesses the body’s own immune system to fight cancer. There is strong evidence that the immune response is a potent weapon against cancer. BCG and levamisole, which act through the active participation of the immune system, have been used as therapies against cancer.1,2 Additional examples of the efficacy of the immune system include tumors that develop following immunosuppressive therapy and respond to withdrawal of that therapy or the tumors that develop in patients with AIDS 3,4 More recent examples of the efficacy of the immune system include vaccine therapies which have resulted in a clinical response in patients with metastatic cancer.5-9 The number of these vaccine approaches has grown with our understanding of the immune response and a wide variety of vaccination schemes have been carried out both in animal models and in human trials. Tumor antigens for these trials have been chosen by a variety of methods. One method is through the evaluation of the specificity of tumor infiltrating lymphocytes. Another approach, and the one we have cho sen, is to use our increased understanding of tumor biology to develop tumor specific antigens. Molecular changes which are unique to the cancer cells have been described. These include mutant proteins and chromosomal translocations with resulting fusion proteins which provide a unique immunologic target. With this in mind, our targets have included the mutant portion of overexpressed and mutated p53 proteins, oncogenic ras mutations, and fusion proteins cre ated by chromosomal translocations specific to pediatric sarcomas. These targets have the addi tional advantage that the mutation or fusion contributes to the malignant phenotype of the cell, so that escape mutations or loss variants cannot occur without loss or reduction of the malignant phenotype.
