Efficient tumor regression induced by genetically engineered tumor cells secreting interleukin-2 and membrane-expressing allogeneic MHC class I antigen.
OBJECTIVE
To analyze the immunotherapeutic potentials of genetically engineered tumor cells secreting IL-2 and a membrane-expressing allogeneic MHC class I molecule Kb in a murine hepatoma model.


METHODS
In order to express both genes in coordination in the target cells, we constructed a polycistronic retroviral vector containing Kb, IL-2, and NeoR genes using two internal ribosome entry sites (IRES). Tumor growth was carried out by implantation of transduced tumor cells into mouse, while anti-tumor effects were demonstrated by the treatment of established tumors. The infiltrated cells were analyzed by immunohistochemistry.


RESULTS
The combined effect of IL-2 secretion and alloantigen expression on immunostimulation was demonstrated by the rejection of transduced tumor cells. In the treatment of established tumors, the Kb/IL-2 co-expressing tumor cells induced strong anti-tumor immunity, superior to that induced by the single gene-transduced cells. The increased diversity of infiltrated cell types in tumor sites indicated that both a specific and non-specific immune response had been activated.


CONCLUSIONS
Our study provides evidence that tumor cells with IL-2 secretion and membrane-expression of allogeneic MHC class I antigen are capable of inducing both strong tumor rejection and immunity.
Qian
S B
SB
Department of Biochemistry and Molecular Biology, Research Center for Human Gene Therapy, Shanghai Second Medical University, PR China. sbqian@shsmu.edu.cn
Li
Y
Y
Qian
G X
GX
Chen
S S
SS
D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008957:Models, Genetic; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy*; D010957:Plasmids / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D007376:Interleukin-2