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PMID: 9862627 Published · ppublish English Clinical Trial Clinical Trial, Phase I Journal Article

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 ·1998-12-16 ·Pages 1894-900

Rosenberg SA, Zhai Y, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Restifo NP, Seipp CA, Einhorn JH, Roberts B, White DE

Abstract

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. 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. 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. 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.

MeSH Terms
Adenoviridae/genetics Antibodies, Viral/blood Antigens, Neoplasm/genetics,immunology Cancer Vaccines/administration & dosage,genetics,immunology Clinical Protocols Humans MART-1 Antigen Melanoma/immunology,prevention & control,secondary Membrane Glycoproteins/biosynthesis,genetics,immunology Neoplasm Proteins/biosynthesis,genetics,immunology Skin Neoplasms/immunology,pathology,prevention & control Treatment Outcome Tumor Cells, Cultured gp100 Melanoma Antigen
Chemicals
Antibodies, Viral Antigens, Neoplasm Cancer Vaccines MART-1 Antigen MLANA protein, human Membrane Glycoproteins Neoplasm Proteins PMEL protein, human gp100 Melanoma Antigen
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Rosenberg S A
Surgery Branch, National Cancer Institute, Bethesda, MD, USA.
Zhai Y
Yang J C
Schwartzentruber D J
Hwu P
Marincola F M
Topalian S L
Restifo N P
Seipp C A
Einhorn J H
Roberts B
White D E
References (46)
46 references, click to expand
  1. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2.
    J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66 PMID: 8028037
  2. Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis.
    Nat Genet. 1994 Sep;8(1):42-51 PMID: 7527271
  3. MHC class I-restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses.
    Immunity. 1994 Aug;1(5):433-42 PMID: 7533647
  4. Recognition of multiple epitopes in the human melanoma antigen gp100 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression.
    J Immunol. 1995 Apr 15;154(8):3961-8 PMID: 7706734
  5. IL-2 enhances the function of recombinant poxvirus-based vaccines in the treatment of established pulmonary metastases.
    J Immunol. 1995 May 15;154(10):5282-92 PMID: 7730632
  6. Adenovirus-mediated gene transfer for cystic fibrosis: quantitative evaluation of repeated in vivo vector administration to the lung.
    Gene Ther. 1994 May;1(3):192-200 PMID: 7584081
  7. Quantitative analysis of repeat adenovirus-mediated gene transfer into injured canine femoral arteries.
    Arterioscler Thromb Vasc Biol. 1995 Dec;15(12):2246-53 PMID: 7489250
  8. Genes coding for tumor antigens recognized by cytolytic T lymphocytes.
    Immunol Rev. 1995 Jun;145:229-50 PMID: 7590828
  9. Therapeutic antitumor response after immunization with a recombinant adenovirus encoding a model tumor-associated antigen.
    J Immunol. 1996 Jan 1;156(1):224-31 PMID: 8598466
  10. Adenovirus vectors as recombinant viral vaccines.
    Vaccine. 1995 Sep;13(13):1143-51 PMID: 8578797
  11. Antigen-specific tumor vaccines. Development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy.
    J Immunol. 1996 Jan 15;156(2):700-10 PMID: 8543823
  12. Immunization against epitopes in the human melanoma antigen gp100 following patient immunization with synthetic peptides.
    Cancer Res. 1996 Oct 15;56(20):4749-57 PMID: 8840994
  13. Humoral and cellular immune responses of nonhuman primates to long-term repeated lung exposure to Ad2/CFTR-2.
    Gene Ther. 1996 Feb;3(2):117-27 PMID: 8867859
  14. Immune responses to viral antigens versus transgene product in the elimination of recombinant adenovirus-infected hepatocytes in vivo.
    Gene Ther. 1996 Feb;3(2):137-44 PMID: 8867861
  15. Circumventing the immune response to adenovirus-mediated gene therapy.
    Gene Ther. 1996 Feb;3(2):154-62 PMID: 8867863
  16. Differential anti-MART-1/MelanA CTL activity in peripheral blood of HLA-A2 melanoma patients in comparison to healthy donors: evidence of in vivo priming by tumor cells.
    J Immunother Emphasis Tumor Immunol. 1996 Jul;19(4):266-77 PMID: 8877721
  17. Development of cancer immunotherapies based on identification of the genes encoding cancer regression antigens.
    J Natl Cancer Inst. 1996 Nov 20;88(22):1635-44 PMID: 8931607
  18. Circumvention of anti-adenovirus neutralizing immunity by administration of an adenoviral vector of an alternate serotype.
    Hum Gene Ther. 1997 Jan 1;8(1):99-109 PMID: 8989999
  19. Established immunity precludes adenovirus-mediated gene transfer in rat carotid arteries. Potential for immunosuppression and vector engineering to overcome barriers of immunity.
    J Clin Invest. 1997 Jan 15;99(2):209-19 PMID: 9005989
  20. Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection.
    Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6458-62 PMID: 8022805
  21. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas.
    J Exp Med. 1994 Jul 1;180(1):35-42 PMID: 8006593
  22. Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes.
    J Exp Med. 1994 Jul 1;180(1):347-52 PMID: 7516411
  23. Adenovirus-mediated gene transfer of soluble vascular cell adhesion molecule to porcine interposition vein grafts.
    Circulation. 1994 May;89(5):1922-8 PMID: 7514108
  24. Enhancement of cellular immunity in melanoma patients immunized with a peptide from MART-1/Melan A.
    Cancer J Sci Am. 1997 Jan-Feb;3(1):37-44 PMID: 9072306
  25. Initial safety and immunogenicity studies of an oral recombinant adenohepatitis B vaccine.
    Vaccine. 1992;10(10):673-6 PMID: 1523878
  26. Immune response to HIV-1 gag antigens induced by recombinant adenovirus vectors in mice and rhesus macaque monkeys.
    J Acquir Immune Defic Syndr. 1991;4(6):568-76 PMID: 1902514
  27. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report.
    N Engl J Med. 1988 Dec 22;319(25):1676-80 PMID: 3264384
  28. Immunization of Canadian Armed Forces personnel with live types 4 and 7 adenovirus vaccines.
    Can J Public Health. 1986 Sep-Oct;77(5):367-70 PMID: 3024797
  29. Control of adenovirus acute respiratory disease in U.S. Army trainees.
    Yale J Biol Med. 1975 Jul;48(3):185-95 PMID: 1099823
  30. Cancer vaccines based on the identification of genes encoding cancer regression antigens.
    Immunol Today. 1997 Apr;18(4):175-82 PMID: 9136454
  31. Human colorectal cancer (CRC) antigen CO17-1A/GA733 encoded by adenovirus inhibits growth of established CRC cells in mice.
    J Immunol. 1997 Jul 15;159(2):763-9 PMID: 9218593
  32. Genetic immunization for the melanoma antigen MART-1/Melan-A using recombinant adenovirus-transduced murine dendritic cells.
    Cancer Res. 1997 Jul 15;57(14):2865-9 PMID: 9230191
  33. Antibody to CD40 ligand inhibits both humoral and cellular immune responses to adenoviral vectors and facilitates repeated administration to mouse airway.
    Gene Ther. 1997 Jun;4(6):611-7 PMID: 9231078
  34. Induction of protective cytotoxic T cell responses in the presence of high titers of virus-neutralizing antibodies: implications for passive and active immunization.
    J Exp Med. 1998 Feb 16;187(4):649-54 PMID: 9463415
  35. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma.
    Nat Med. 1998 Mar;4(3):321-7 PMID: 9500606
  36. The development of new cancer therapies based on the molecular identification of cancer regression antigens.
    Cancer J Sci Am. 1995 Jul-Aug;1(2):90-100 PMID: 9166458
  37. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor.
    Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9 PMID: 8170938
  38. Safety and efficacy of repetitive adenovirus-mediated transfer of CFTR cDNA to airway epithelia of primates and cotton rats.
    Nat Genet. 1994 Jan;6(1):75-83 PMID: 7511023
  39. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2.
    JAMA. 1994 Mar 23-30;271(12):907-13 PMID: 8120958
  40. The advent of adenovirus. Gene therapy for cardiovascular disease.
    Circulation. 1993 Oct;88(4 Pt 1):1937-42 PMID: 8403339
  41. Hepatic gene therapy: efficient gene delivery and expression in primary hepatocytes utilizing a conjugated adenovirus-DNA complex.
    Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11548-52 PMID: 8265587
  42. Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis.
    Cell. 1993 Oct 22;75(2):207-16 PMID: 7691415
  43. Development and analysis of recombinant adenoviruses for gene therapy of cystic fibrosis.
    Hum Gene Ther. 1993 Aug;4(4):461-76 PMID: 7691187
  44. Gene therapy: adenovirus vectors.
    Curr Opin Genet Dev. 1993 Jun;3(3):499-503 PMID: 8353427
  45. Immunogenicity of recombinant human adenovirus-human immunodeficiency virus vaccines in chimpanzees.
    AIDS Res Hum Retroviruses. 1993 May;9(5):395-404 PMID: 8318268
  46. Diversity of airway epithelial cell targets for in vivo recombinant adenovirus-mediated gene transfer.
    J Clin Invest. 1993 Jan;91(1):225-34 PMID: 8423221
Article Info
Journal
Journal of the National Cancer Institute
Abbr.
J Natl Cancer Inst
ISSN
0027-8874
DOI
10.1093/jnci/90.24.1894
Published
1998-12-16
Pages
1894-900
Language
English
Region
United States
NLM ID
7503089
PMCID
PMC2249697
Subset
IM
Grants
Intramural NIH HHS · Z01 BC010763-01 · United States
Intramural NIH HHS · Z99 CA999999 · United States
External Links
PubMed source DOI: 10.1093/jnci/90.24.1894 PMC Full Text View journal details
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