The immunotherapy of solid cancers based on cloning the genes encoding tumor-rejection antigens

Cellular immune reactions play a major role in the host reaction to growing cancers. Tumor infiltrating lymphocytes (TIL) can be isolated from melanomas and can specifically recognize unique tumor antigens. The adoptive transfer of TIL plus interleukin-2 can mediate tumor regression in patients with metastatic melanoma. TIL capable of mediating tumor regression have been used to clone and sequence a variety of the genes that encode the tumor-regression antigens recognized by these TIL. This information has opened new opportunities for the development of cancer immunotherapies. These gene products can be used to generate lymphocytes, in vitro, with improved antitumor activity for use in adoptive transfer. Active immunization can be performed using either the immunodominant peptides present in these proteins or by incorporating the tumor antigen genes into recombinant viruses. Cancer vaccine trials using many of these approaches have recently begun. Attempts to apply a similar strategy to epithelial tumors such as breast and ovarian cancer are underway.