This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Prabakaran, I. Articles by Fraker, D. L. Search for Related Content PubMed PubMed Citation Articles by Prabakaran, I. Articles by Fraker, D. L.

Mature CD83⁺ Dendritic Cells Infected With Recombinant gp100 Vaccinia Virus Stimulate Potent Antimelanoma T Cells

From the Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania (IP, CM, SX, BJC, DLF); and Therion Biologics Corporation, Cambridge, Massachusetts (AG-Y).

Correspondence: Address correspondence and reprint requests to: Douglas Fraker, MD, Department of Surgery, 4th Floor, Silverstein Building, 3400 Spruce St., Philadelphia, PA 19104; Fax: 215-614-0765; E-mail: fraker{at}mail.med.upenn.edu

Background: Mature dendritic cells (DCs) are potent antigen-presenting cells that activate naive T lymphocytes and initiate cellular immune responses. The ability of CD83⁺ mature DCs infected with vaccinia virus encoding the gp100 melanoma transgene (rV-gp100) to stimulate an antimelanoma CD8⁺ T-cell response was investigated.

Methods: Monocyte-derived immature or CD83⁺ mature DCs were infected with rV-gp100. The activation state of the DCs and the expression of gp100 protein were evaluated by flow cytometry. The reactivity of antimelanoma CD8⁺ T cells was confirmed by measuring specific interferon secretion by using enzyme-linked immunosorbent assay in a mixed-tumor lymphocyte culture.

Results: Both immature and CD83⁺ mature DCs expressed gp100 protein when the DCs were infected with rV-gp100. Calcium-signaling agents were required to induce maturation of both infected and noninfected immature DCs. Only rV-gp100-infected CD83⁺ DCs induced CD8⁺ T cells, after a single stimulation that recognized both peptide-pulsed target cells to multiple gp100 epitopes and a melanoma cell line that endogenously expressed gp100 antigen.

Conclusions: CD83⁺ DCs transduced with rV-gp100 are capable of generating a strong CD8⁺ T-cell response against melanoma tumor cells. Expression of melanoma antigens by mature DCs offers the potential advantage of presenting multiple endogenously processed T-cell epitopes and using multiple HLA restriction elements for antimelanoma vaccine therapy.

Key Words: Melanoma • Dendritic cells • Tumor-associated antigen • gp100 • Vaccinia virus • CD8⁺