Dendritic cells infected with poxviruses encoding MART-1/Melan A sensitize T lymphocytes in vitro

Christina J. Kim, Tracy Prevette, Janice Cormier, Willem Overwijk, Matthew Roden, Nicholas P. Restifo, Steven A. Rosenberg, Francesco M. Marincola

Research output: Contribution to journalArticle

Abstract

Dendritic cells (DC) are potent professional antigen-presenting cells that can activate naive T lymphocytes and initiate cellular immune responses. As adjuvants, DC may be useful in enhancing the immunogenicity of tumor antigens and mediating tumor regression. Endogenous expression of antigen by DC offers the potential advantage of allowing prolonged constitutive presentation of endogenously processed epitopes and exploitation of multiple restriction elements for the presentation of the same antigen. In this report, we show that human DC are (a) capable of infection by recombinant poxviruses encoding melanoma-associated antigen (MAA) genes and (b) capable of efficiently processing and presenting these MAA to cytotoxic T cells. In 6/6 HLA A*0201-expressing melanoma patients tested, the virally driven expression of MART-1/Melan A MAA by DC was sufficient to generate CD8+ T lymphocytes that could recognize naturally processed epitopes on tumor cells. In most cases, specific anti-MART-1 reactivity could be detected after a single stimulation. Analysis of epitope dominance revealed that the amino acid sequence recognized by these cytotoxic T lymphocytes (CTL) corresponded to the MART-127.35 residues previously shown to be most commonly recognized by cytotoxic T lymphocytes expanded from metastatic melanoma lesions. These data show that the vitally driven expression of MAA by DC can be exploited for the efficient induction of clinically relevant cytotoxic T- cell responses. This has clinical implications for active immunization therapy, and currently vaccine trials have been proposed for patients with metastatic melanoma.

Original languageEnglish (US)
Pages (from-to)276-286
Number of pages11
JournalJournal of Immunotherapy
Volume20
Issue number4
DOIs
StatePublished - 1997
Externally publishedYes

Fingerprint

MART-1 Antigen
Poxviridae
Dendritic Cells
Melanoma-Specific Antigens
T-Lymphocytes
Epitopes
Melanoma
Cytotoxic T-Lymphocytes
Poxviridae Infections
Active Immunotherapy
Antigen Presentation
Neoplasm Antigens
Antigen-Presenting Cells
Cellular Immunity
In Vitro Techniques
Amino Acid Sequence
Neoplasms
Vaccination
Antigens
Genes

Keywords

  • CTL
  • Dendritic cells
  • MART-1
  • Melanoma
  • Melanoma-associated antigens
  • Pox viruses
  • Viral vectors

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Kim, C. J., Prevette, T., Cormier, J., Overwijk, W., Roden, M., Restifo, N. P., ... Marincola, F. M. (1997). Dendritic cells infected with poxviruses encoding MART-1/Melan A sensitize T lymphocytes in vitro. Journal of Immunotherapy, 20(4), 276-286. https://doi.org/10.1097/00002371-199707000-00004

Dendritic cells infected with poxviruses encoding MART-1/Melan A sensitize T lymphocytes in vitro. / Kim, Christina J.; Prevette, Tracy; Cormier, Janice; Overwijk, Willem; Roden, Matthew; Restifo, Nicholas P.; Rosenberg, Steven A.; Marincola, Francesco M.

In: Journal of Immunotherapy, Vol. 20, No. 4, 1997, p. 276-286.

Research output: Contribution to journalArticle

Kim, CJ, Prevette, T, Cormier, J, Overwijk, W, Roden, M, Restifo, NP, Rosenberg, SA & Marincola, FM 1997, 'Dendritic cells infected with poxviruses encoding MART-1/Melan A sensitize T lymphocytes in vitro', Journal of Immunotherapy, vol. 20, no. 4, pp. 276-286. https://doi.org/10.1097/00002371-199707000-00004
Kim, Christina J. ; Prevette, Tracy ; Cormier, Janice ; Overwijk, Willem ; Roden, Matthew ; Restifo, Nicholas P. ; Rosenberg, Steven A. ; Marincola, Francesco M. / Dendritic cells infected with poxviruses encoding MART-1/Melan A sensitize T lymphocytes in vitro. In: Journal of Immunotherapy. 1997 ; Vol. 20, No. 4. pp. 276-286.
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