© 1998 by Oxford University Press
Journal Of The National Cancer Institute, Vol 90, 1894-1900, Copyright © 1998 by Oxford University Press
SA Rosenberg, Y Zhai, JC Yang, DJ Schwartzentruber, P Hwu, FM Marincola, SL Topalian, NP Restifo, CA Seipp, JH Einhorn, B Roberts and DE White
BACKGROUND: The characterization of the genes encoding melanoma- associated
antigens MART-1 or gp100, recognized by T cells, has opened new
possibilities for 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 10(7) and 10(11) 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 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 safely administered to
cancer patients. High levels of neutralizing antibody present in patients'
sera prior to treatment may have impaired the ability of these viruses to
immunize patients against melanoma antigens.
ARTICLES
Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens
Surgery Branch, National Cancer Institute, Bethesda, MD, USA.
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