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Mature CD83+ dendritic cells infected with recombinant gp 100 vaccinia virus stimulate potent antimelanoma T cells

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Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Mature dendritics 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 gp 100 melanoma transgene (rV-gp 100) 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 gp 100 protein were evaluated by flow cytometry. The reactivity of antimelanoma CD8+ T cells was confirmed by measuring specific interferon γ secretion by using enzyme-linked immunosorbent assay in a mixed-tumor lymphocyte culture.

Results

Both immature and CD83+ mature DCs expressed gp 100 protein when the DCs were infected with rV-gp 100. Calcium-signaling agents were required to induce maturation of both infected and nonifected 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 gp 100 epitopes and a melanoma cell line that endogenously expressed gp 100 antigen.

Conclusions

CD83+ DCs transduced with rV-gp 100 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-cells epitopes and using multiple HLA restriction elements for antimelanoma vaccine therapy.

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Authors and Affiliations

  1. Department of Surgery, University of Pennsylvania, 4th Floor, Silverstein Building, 3400 Spruce St., 19104, Philadelphia, PA

    Indira Prabakaran MSc, Chandrakala Menon PhD, Shuwen Xu MD, Brian J. Czerniecki MD, PhD & Douglas L. Fraker MD

  2. Therion Biologics Corporation, Cambridge, Massachusetts

    Alicia Gómez-Yafal PhD

Authors
  1. Indira Prabakaran MSc
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  2. Chandrakala Menon PhD
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  3. Shuwen Xu MD
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  4. Alicia Gómez-Yafal PhD
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  5. Brian J. Czerniecki MD, PhD
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  6. Douglas L. Fraker MD
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Correspondence to Douglas L. Fraker MD.

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Prabakaran, I., Menon, C., Xu, S. et al. Mature CD83+ dendritic cells infected with recombinant gp 100 vaccinia virus stimulate potent antimelanoma T cells. Annals of Surgical Oncology 9, 411–418 (2002). https://doi.org/10.1007/BF02573878

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  • DOI: https://doi.org/10.1007/BF02573878

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