T-cells represent the most potent effector arm for the rejection of cancer in response to immunostimulation. In order to understand and augment this effector function, it is necessary to develop methods for generating tumor-reactive T-cells and then augment these pathways through the manipulation of normal immune response pathways. Dendritic cells (DC) represent the master antigen presenting cell and their biology is being rapidly elucidated. Ways to exploit this information and to use them to present whole tumor cells would result in T-cell responses with the greatest potency and breadth. We are currently using renal cancer as a model (wherein tumor is readily available and immunotherapy is known to be effective in some patients) to explore the efficient generation of tumor-reactive T-cells using DC and tumor cells as the stimulus. Preliminary work has shown this to be a very fruitful avenue in that 7 or 7 patients thusfar studied using autologous DC, autologous tumor and autologous PBMC have produced tumor-reactive T-cells suitable for antigen discovery and possibly future adoptive cell therapy. The use of tumor apoptotic bodies as the source of antigen has been most effective and this has produced both CD4 and CD8-restricted T-cells in most patients. Future studies are focusing on defining further stimuli (especially the ligands of Toll-like receptors) as means of improving these T-cell responses.
Hanada, Ken-Ichi; Yewdell, Jonathan W; Yang, James C (2004) Immune recognition of a human renal cancer antigen through post-translational protein splicing. Nature 427:252-6 |
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