Human dendritic cells genetically engineered to express high levels of the human epithelial tumor antigen mucin (MUC-1).
We have achieved stable high-level expression of a human tumor antigen, epithelial cell mucin (MUC-1), on human dendritic cells (DCs) by retroviral transduction of CD34+ progenitor cells and their subsequent cytokine-induced differentiation into DCs. The process of retroviral transduction did not alter the growth or differentiation of DCs from CD34+ progenitor cells. Immunofluorescence and electron microscopy studies revealed that the expression of mucin was limited to the body of the DCs and was excluded from the cytoplasmic veils of the DCs. Furthermore, the expression of mucin on DCs was similar, if not identical, to the nonpolarized expression of mucin found on carcinoma cells. In functional studies, the MUC-1(+)-transduced DCs were potent stimulators of allogeneic CD4+ T cells and, in fact, were superior to MUC-1- DCs. Thus, MUC-1+ DCs are expected to be a valuable tool in the immunotherapeutic treatment of patients with tumors that express MUC-1.
Henderson
R A
RA
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Nimgaonkar
M T
MT
Watkins
S C
SC
Robbins
P D
PD
Ball
E D
ED
Finn
O J
OJ
D018952:Antigens, CD34 / Q000032:analysis; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000378:metabolism*; D005818:Genetic Engineering; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation; D018396:Mucin-1 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology
D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D018396:Mucin-1