Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens

Background: The characterization of the genes encoding melanoma-associated antigens MART-1 or gp100, recognized by T cells, has opened new possibiliti es for the development of immunization strategies for patients with metasta tic melanoma, With the use of recombinant adenoviruses expressing either MA RT-1 or gp100 to immunize patients with metastatic melanoma, we evaluated t he safety, immunologic, and potential therapeutic aspects of these immuniza tions. Methods: In phase I studies, 54 patients received escalating doses ( between 10(7) and 10(11) plaque-forming units) of recombinant adenovirus en coding either MART-1 or gp100 melanoma antigen administered either alone or followed by the administration of interleukin 2 (IL-2). The immunologic im pact of these immunizations on the development of cellular and antibody rea ctivity was assayed. Results: Recombinant adenoviruses expressing MART-1 or gp100 were safely administered. One of 16 patients with metastatic melanom a receiving the recombinant adenovirus MART-1 alone experienced a complete response. Other patients achieved objective responses, but they had receive d IL-2 along with an adenovirus, and their responses could be attributed to the cytokine, Immunologic assays showed no consistent immunization to the MART-1 or gp100 transgenes expressed by the recombinant adenoviruses. High levels of neutralizing antibody were found in the pretreatment sera of the patients. Conclusions: High doses of recombinant adenoviruses could be safe ly administered to cancer patients. High levels of neutralizing antibody pr esent in patients' sera prior to treatment may have impaired the ability of these viruses to immunize patients against melanoma antigens.