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Enhancement of antitumor immunity by prolonging antigen presentation on dendritic cells

Nature Biotechnology volume 20, pages 149154 (2002) | Download Citation

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Abstract

Vaccination with dendritic cells (DCs) pulsed with antigenic peptides derived from various tumor antigens has great, but as yet significantly unrealized, potential in cancer treatment. Here, we describe a strategy for prolonged presentation of an MHC class I–restricted self-peptide on DCs through linkage of it to a cell penetrating peptide (CPP). DCs loaded with a peptide derived from tyrosinase-related protein 2 (TRP2) covalently linked to a CPP1 sequence retained full capacity to stimulate T cells for at least 24 h, completely protected immunized mice from subsequent tumor challenge, and significantly inhibited lung metastases in a 3-day tumor model. DCs pulsed with TRP2 alone failed to provide any of these protections. In addition, we demonstrate that both CD4+ and CD8+ T cells were required for potent antitumor immunity. This CPP-based approach may be generally applicable to enhance the efficacy of DC-based peptide vaccines against cancer and other diseases.

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Acknowledgements

We thank Malcolm Brenner for his helpful suggestions and critical reading of the manuscript and Tihui Fu for assistance in some experiments.

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Affiliations

  1. The Center for Cell and Gene Therapy and Department of Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.

    • Rong-Fu Wang
    •  & Helen Y. Wang

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Correspondence to Rong-Fu Wang.

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    Web Figure 1.

    Phenotype characterization and MLR assay of DCs. A) Surface phenotype of mature and immature DCs generated different culture conditions. DCs were stained anti-CD11c-PE along with anti-I-A-FITC, anti-B7-1-FITC and anti-B7-2-FITC, respectively, and analyzed by flow cytometry. Double positive staining of mutaure DC for CD11c and co-stimulatory B7.1, B7.2 and MHC class II molecules was 55-70% while double positive staining for immature DC was only about 15-20%. B) Allogeneic MLR of mature, immature DCs and splenocytes. DCs were cocultured with allogeneic BALB/c T cells isolated from bulk splenocytes by passing cell through an immunoaffinity column. [3H]-thymidine incorporation from triplicate wells were obtained after subtraction of the background counts from irradiated stimulators and T cells alone, and are plotted as the average counts for each stimulator:effector ratio.

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https://doi.org/10.1038/nbt0202-149

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