PMID- 8971174
OWN - NLM
STAT- MEDLINE
DCOM- 19970123
LR  - 20061115
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 56
IP  - 24
DP  - 1996 Dec 15
TI  - Retroviral transduction of human dendritic cells with a tumor-associated antigen 
      gene.
PG  - 5672-7
AB  - 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.
FAU - Reeves, M E
AU  - Reeves ME
AD  - Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
FAU - Royal, R E
AU  - Royal RE
FAU - Lam, J S
AU  - Lam JS
FAU - Rosenberg, S A
AU  - Rosenberg SA
FAU - Hwu, P
AU  - Hwu P
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Epitopes)
SB  - IM
MH  - Antigens, Neoplasm/*genetics/immunology
MH  - Dendritic Cells/*immunology
MH  - Epitopes/*genetics/immunology
MH  - Genetic Vectors/*genetics/immunology
MH  - Humans
MH  - Immunity, Cellular
MH  - Lymphocytes, Tumor-Infiltrating/*immunology
MH  - Melanoma/*immunology/therapy
MH  - Retroviridae/*genetics
MH  - Transfection/genetics/*methods
EDAT- 1996/12/15 00:00
MHDA- 1996/12/15 00:01
CRDT- 1996/12/15 00:00
PHST- 1996/12/15 00:00 [pubmed]
PHST- 1996/12/15 00:01 [medline]
PHST- 1996/12/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1996 Dec 15;56(24):5672-7.