Retrovirally transduced human dendritic cells express a normal phenotype and potent T-cell stimulatory capacity Journal Article
| Authors: | Szabolcs, P.; Gallardo, H. F.; Ciocon, D. H.; Sadelain, M.; Young, J. W. |
| Article Title: | Retrovirally transduced human dendritic cells express a normal phenotype and potent T-cell stimulatory capacity |
| Abstract: | Dendritic cells are attractive candidates for vaccine-based immunotherapy because of their potential to function as natural adjuvants for poorly immunogenic proteins derived from tumors or microbes. In this study, we evaluated the feasibility and consequences of introducing foreign genetic material by retroviral vectors into dendritic cell progenitors. Proliferating human bone marrow and cord blood CD34+ cells were infected by retrovital vectors encoding the murine CD2 surface antigen. Mean transduction efficiency in dendritic cells was 11.5% from bone marrow and 21.2% from cord blood progenitors. Transduced or untransduced dendritic cell progeny expressed comparable levels of HLA-DR, CD83, CD1a, CD80, CD86, S100, and p55 antigens. Granulocytes, macrophages, and dendritic cells were equally represented among the transduced and mock-transduced cells, thus showing no apparent alteration in the differentiation of transduced CD34+ precursors. The T-cell stimulatory capacity of retrovirally modified and purified mCD2-positive allogeneic or nominal antigen-pulsed autologous dendritic cells was comparable with that of untransduced dendritic cells, human CD34+ dendritic cell progenitors can therefore be efficiently transduced using retroviral vectors and can differentiate into potent immunostimulatory dendritic cells without compromising their T-cell stimulators, capacity or the expression of critical costimulatory molecules and phenotypic markers. These results support ongoing efforts to develop genetically modified dendritic cells for immunotherapy. |
| Keywords: | controlled study; human cell; flow cytometry; antigen expression; t-lymphocytes; bone marrow cells; cd34 antigen; dendritic cell; clinical protocol; genetic transduction; genetic vectors; transduction, genetic; cd2 antigen; lymphocyte activation; dendritic cells; fetal blood; immunotherapy; genetic engineering; immunogenicity; hla dr antigen; hematopoietic stem cells; umbilical cord blood; protein s 100; immunophenotyping; immunostimulation; hematopoietic stem cell; antigens, cd34; antigen presenting cell; antigen-presenting cells; t lymphocyte activation; b7 antigen; cd86 antigen; retrovirus; virus vector; leukemia virus, murine; antigens, cd2; humans; human; priority journal; article; superantigens |
| Journal Title: | Blood |
| Volume: | 90 |
| Issue: | 6 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 1997-09-15 |
| Start Page: | 2160 |
| End Page: | 2167 |
| Language: | English |
| PUBMED: | 9310466 |
| PROVIDER: | scopus |
| DOI: | 10.1182/blood.V90.6.2160 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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