Dendritic cells loaded with MART-1 peptide or infected with adenoviral construct are functionally equivalent in the induction of tumor-specific cytotoxic T lymphocyte responses in patients with melanoma
R. Philip et al., Dendritic cells loaded with MART-1 peptide or infected with adenoviral construct are functionally equivalent in the induction of tumor-specific cytotoxic T lymphocyte responses in patients with melanoma, J IMMUNOTH, 23(1), 2000, pp. 168-176
Immunization with tumor-specific-associated antigen-pulsed dendritic cells
has proved to be efficacious in various animal models and is being evaluate
d for the treatment of cancer in humans. Use of dendritic cells pulsed with
specific peptides or transfected with tumor-associated antigen genes has b
een a focused area of investigation for inducing potent tumor and viral imm
une responses. In this study, the authors demonstrate transgene expression,
including the lacZ and MART-1 genes, in dendritic cells infected with aden
oviral constructs. These transiently transduced dendritic cells, derived fr
om melanoma patients' monocytes cultured with granulocyte-macrophage colony
-stimulating factor and interleukin-4, express the transgene and can stimul
ate patients' CD8(+) T cells to elicit an antitumor immune response compara
ble to dendritic cells loaded with a defined peptide. These cytotoxic T lym
phocytes were able to recognize both known and unknown tumor-associated ant
igen epitopes and exhibited cytolytic activity against HLA-matched tumor ce
lls expressing the antigen. The ability to induce tumor-specific cytotoxic
T lymphocytes in vitro using gene-modified dendritic cells that transiently
express tumor-associated antigens demonstrates the potential use of these
antigen-presenting cells for developing in vivo cancer vaccines.