Journal Article

Immunizing Patients With Metastatic Melanoma Using Recombinant Adenoviruses Encoding MART-1 or gp100 Melanoma Antigens

Steven A. Rosenberg, Yifan Zhai, James C. Yang, Douglas J. Schwartzentruber, Patrick Hwu, Francesco M. Marincola, Suzanne L. Topalian, Nicholas P. Restifo, Claudia A. Seipp, Jan H. Einhorn, Donald E. White and Bruce Roberts

in JNCI: Journal of the National Cancer Institute

Volume 90, issue 24, pages 1870-1872
Published in print December 1998 | ISSN: 0027-8874
Published online December 1998 | e-ISSN: 1460-2105 | DOI: http://dx.doi.org/10.1093/jnci/90.24.1894
Immunizing Patients With Metastatic Melanoma Using Recombinant Adenoviruses Encoding MART-1 or gp100 Melanoma Antigens

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Background: The characterization of the genes encoding melanoma-associated antigens MART-1 or gp100, recognized by T cells, has opened new possibilitiesfor the development of immunization strategies for patients with metastatic melanoma. With the use of recombinant adenoviruses expressing either MART-1 or gp100 to immunize patients with metastatic melanoma, we evaluated the safety, immunologic, and potential therapeutic aspects of these immunizations. Methods: In phase I studies, 54 patients received escalating doses (between 107 and 1011 plaque-forming units) of recombinant adenovirus encoding either MART-1 or gp100 melanoma antigen administered either alone or followed by the administration of interleukin 2 (IL-2). The immunologic impact of these immunizations on the development of cellular and antibody reactivity was assayed. Results: Recombinant adenoviruses expressing MART-1 or gp100 were safely administered. One of 16 patients with metastatic melanoma receiving the recombinant adenovirus MART-1 alone experienced a complete response. Other patients achieved objective responses, but they had received IL-2 along with an adenovirus, and their responses could be attributed to the cytokine. Immunologic assays showed noconsistent immunization to the MART-1 or gp100 transgenes expressed by the recombinant adenoviruses. High levels of neutralizing anti-body were found in the pretreatment sera of the patients. Conclusions: High doses of recombinant adenoviruses could be safely administered to cancer patients. High levels of neutralizing anti-body present in patients' sera prior to treatment may have impaired the ability of these viruses to immunize patients against melanoma antigens.

Journal Article.  5374 words.  Illustrated.

Subjects: Medical Oncology

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