Use of KBMA Listeria monocytogenes as an antigen loading platform for dendritic cell-mediated induction of antitumor immunity
2008
3044 Background: Melanoma is one of the most rapidly growing cancers worldwide yet there is no satisfactory treatment. Dendritic cells (DC) are attractive cellular adjuvants which can increase host resistance to tumor. To optimally prime naive T cells, DCs must not only present high levels of MHC-peptide complexes, but must also undergo activation and maturation. Methods: The highly attenuated killed but metabolically active (KBMA) Listeria monocytogenes (Lm) were engineered to express the HLA-A*0201 CD8+ T cell epitopes of melanoma-associated antigen (MAA) MelanA/Mart-1 and of control influenza matrix protein, both encoded within the OVA scaffold protein. These bacteria served as a DC antigen-loading platform. Monocyte-derived DC were generated from PBMCs of healthy donors, infected with recombinant attenuated KBMA Lm (rLm) and evaluated for maturation and presentation of the tumor-specific epitope. These DC were also used to generate tumor-specific CD8+ T cell lines, which were tested for effector poten...
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