0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Retroviral transduction of human dendritic cells with a tumor-associated antigen gene.

      Cancer research

      Read this article at

      ScienceOpenPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Dendritic cells (DCs) are potent antigen-presenting cells that can activate quiescent T lymphocytes. When pulsed with tumor-associated antigen (TAA) peptide or protein, murine DCs can provide antitumor immunity. We reasoned that DCs retrovirally transduced with TAA genes might have important advantages over peptide- or protein-pulsed DCs, including long-term TAA presentation in vivo, and presentation of important but undefined epitopes. Therefore, we attempted to retrovirally transduce human DCs with a melanoma TAA gene (MART-1) and determine whether these transduced DCs could raise a specific antitumor response from quiescent autologous T lymphocytes. After retroviral transduction, human CD34+ cells were differentiated into DCs in vitro using granulocyte macrophage colony-stimulating factor, tumor necrosis factor alpha, and stem cell factor. This method consistently yielded a population of DCs as analyzed by morphology, phenotype, and MLR. Flow cytometric analysis revealed that 22-28% of cells expressing the DC phenotype also expressed a transduced marker gene. When DCs were transduced with the gene encoding MART-1, they stimulated much higher levels of cytokine release by MART-1-specific tumor-infiltrating lymphocytes than control DCs transduced with an irrelevant gene. In vitro stimulation using MART-1-transduced DCs but not control-transduced DCs raised specific antitumor CTLs from autologous quiescent T cells. These results provide evidence that human DCs can be retrovirally transduced with a TAA gene and that these transduced cells can raise a specific antitumor immune response in vitro. Transduced DCs may be useful for in vivo immunization against TAA.

          Related collections

          Author and article information

          Journal
          8971174

          Comments

          Comment on this article