Melanoma vaccines: prospects for the treatment of melanoma.
A number of melanoma vaccines, made from whole melanoma cells or components of melanoma cells, are being tested in Phase II or III trials in patients after surgical removal of high risk primary or regional lymph node metastases, or in those with disseminated melanoma. During the progress of these trials, a number of melanoma antigens and their peptide epitopes that are recognised by human T-cells have been described. These findings and new information about antigen recognition by human T-cells have made it possible to explore the use of peptide epitopes targeted at T-cells as melanoma vaccines. Preliminary results are encouraging and suggest that it may soon be possible to use well defined vaccines, selected on the basis of the antigenic phenotype of the patient's melanoma and their HLA status. Equally exciting advances have been made preparing and using recombinant viral vectors containing genes that code for melanoma antigens. Experimental studies on the use of naked DNA as vaccines are also proceeding. Several fundamental obstacles preventing the effective use of T-cell epitope vaccines remain. These include selection of HLA and tumour antigen loss variants by the immune system, and conditioning of an ineffective immune response by the growing tumour. These aspects suggest that the development of effective vaccine therapy in the future may require a combination of strategies designed to stimulate HLA-restricted and -non-restricted effector cells, and judicious use of cytokines to obtain an effective immune response.
Hersey
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Oncology & Immunology Unit, Department of Surgery, John Hunter Hospital, Room 443, David Maddison Clinical Sciences Building, Cnr.King & Watt Street, Newcastle, NSW2300, Australia.