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 Topalian, Nicholas P. Restifo, Claudia A. Seipp, Jan H. Einhorn, Bruce Roberts, Donald E. White

Research output: Contribution to journalArticle

Abstract

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 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 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.

Original languageEnglish (US)
Pages (from-to)1894-1900
Number of pages7
JournalJournal of the National Cancer Institute
Volume90
Issue number24
StatePublished - Dec 16 1998
Externally publishedYes

Fingerprint

gp100 Melanoma Antigen
Adenoviridae
Melanoma
Immunization
Melanoma-Specific Antigens
Neutralizing Antibodies
Interleukin-2
Serum
Transgenes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rosenberg, S. A., Zhai, Y., Yang, J. C., Schwartzentruber, D. J., Hwu, P., Marincola, F. M., ... White, D. E. (1998). Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens. Journal of the National Cancer Institute, 90(24), 1894-1900.

Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens. / Rosenberg, Steven A.; Zhai, Yifan; Yang, James C.; Schwartzentruber, Douglas J.; Hwu, Patrick; Marincola, Francesco M.; Topalian, Suzanne; Restifo, Nicholas P.; Seipp, Claudia A.; Einhorn, Jan H.; Roberts, Bruce; White, Donald E.

In: Journal of the National Cancer Institute, Vol. 90, No. 24, 16.12.1998, p. 1894-1900.

Research output: Contribution to journalArticle

Rosenberg, SA, Zhai, Y, Yang, JC, Schwartzentruber, DJ, Hwu, P, Marincola, FM, Topalian, S, Restifo, NP, Seipp, CA, Einhorn, JH, Roberts, B & White, DE 1998, 'Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens', Journal of the National Cancer Institute, vol. 90, no. 24, pp. 1894-1900.
Rosenberg SA, Zhai Y, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM et al. Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens. Journal of the National Cancer Institute. 1998 Dec 16;90(24):1894-1900.
Rosenberg, Steven A. ; Zhai, Yifan ; Yang, James C. ; Schwartzentruber, Douglas J. ; Hwu, Patrick ; Marincola, Francesco M. ; Topalian, Suzanne ; Restifo, Nicholas P. ; Seipp, Claudia A. ; Einhorn, Jan H. ; Roberts, Bruce ; White, Donald E. / Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens. In: Journal of the National Cancer Institute. 1998 ; Vol. 90, No. 24. pp. 1894-1900.
@article{3ccf25094f364ab1a299faa0c5fe8081,
title = "Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens",
abstract = "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 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 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.",
author = "Rosenberg, {Steven A.} and Yifan Zhai and Yang, {James C.} and Schwartzentruber, {Douglas J.} and Patrick Hwu and Marincola, {Francesco M.} and Suzanne Topalian and Restifo, {Nicholas P.} and Seipp, {Claudia A.} and Einhorn, {Jan H.} and Bruce Roberts and White, {Donald E.}",
year = "1998",
month = "12",
day = "16",
language = "English (US)",
volume = "90",
pages = "1894--1900",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "24",

}

TY - JOUR

T1 - Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens

AU - Rosenberg, Steven A.

AU - Zhai, Yifan

AU - Yang, James C.

AU - Schwartzentruber, Douglas J.

AU - Hwu, Patrick

AU - Marincola, Francesco M.

AU - Topalian, Suzanne

AU - Restifo, Nicholas P.

AU - Seipp, Claudia A.

AU - Einhorn, Jan H.

AU - Roberts, Bruce

AU - White, Donald E.

PY - 1998/12/16

Y1 - 1998/12/16

N2 - 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 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 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.

AB - 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 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 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.

UR - http://www.scopus.com/inward/record.url?scp=0032539190&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032539190&partnerID=8YFLogxK

M3 - Article

C2 - 9862627

AN - SCOPUS:0032539190

VL - 90

SP - 1894

EP - 1900

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 24

ER -