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Philip, R. et al.

Philip, Brunette, Ashton, Alters, Gadea, Sorich, Yau, O'Donoghue, Lebkowski, Okarma, Philip,

Transgene expression in dendritic cells to induce antigen-specific cytotoxic T cells in healthy donors.

Immunization with specific tumor-associated antigen (Ag) (TAA)-pulsed dendritic cells (DC) has proven to be efficacious in a variety of animal models and is being investigated for the treatment of cancer patients. Use of DC pulsed with specific peptides or transfected with TAA genes has been a focused area of investigation for the induction of potent tumor and viral immune responses. In this study we demonstrate transgene expression, including expression of the MART-1 gene, in DC transfected with plasmid DNA and cationic liposome complexes. These transiently transfected DC, derived from healthy donor monocytes cultured with granulocyte macrophage colony-stimulating factor and interleukin-4, express the transgene and can stimulate naive CD8+ T cells to elicit an antitumor immune response. These cytotoxic T lymphocytes (CTL) were capable of recognizing both known and unknown TAA epitopes and were able to exhibit cytolytic activity against human histocompatibility leukocyte Ag-matched tumor cells expressing the Ag. In addition to their cytolytic function, the CTL displayed an oligoclonal T-cell receptor repertoire, indicating that the presented Ag induced alterations in the T-cell population. The ability to induce tumor-specific CTL in vitro using gene-modified DC transiently expressing TAAs demonstrates the potential use of these Ag-presenting cells to generate future in vivo cancer vaccine strategies.[1]

References

Transgene expression in dendritic cells to induce antigen-specific cytotoxic T cells in healthy donors. Philip, R., Brunette, E., Ashton, J., Alters, S., Gadea, J., Sorich, M., Yau, J., O'Donoghue, G., Lebkowski, J., Okarma, T., Philip, M. Cancer Gene Ther. (1998) [Pubmed]

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