May 2002

From Journal of Clinical Investigation

Tumor vaccines via dendritic cells

Dendritic cells (DCs) can process and present tumor cell-specific antigens, activating CD8+ T lymphocytes to destroy tumor cells. Here, Wang and colleagues propose a new route to tumor antigen presentation that they hope will help realize he promise of DC vaccines for treating cancer or blocking metastatic disease. In their method, an appropriate MHC-restricted epitope is generated as a fusion peptide carrying an additional, HIV-derived sequence that allows it to penetrate the DC plasma membrane. Wang et al. have found that such fusion peptides are taken up more readily and presented by DC more efficiently than occurs following standard DC ?pulsing? protocols. Now, they show that this quantitative change in tumor antigen presentation correlates with a qualitative improvement in T cell tumoricidal activity. Working with a peptide that serves as a tumor antigen in both humans and mice, the authors find that transduced DC activate both CD4+ and CD8+ cells, which act synergistically to suppress tumor in mice carrying metastatic melanoma cells. The contribution of CD4+ cells to this process was not anticipated and remains something of a puzzle, since the tumor antigen used is restricted by Class I MHC molecules, which activate CD8+ cells. Nonetheless, control mice receiving the peptide-transduced DC appear to be completely protected from metastatic disease, while animals lacking either the CD4+ or CD8+ subtype develop a significant number of lung metastases. This procedure seems well suited for DC vaccination in vitro or in vivo, using cell-permeant forms of this or other tumor antigens. Still, concerns about provoking autoimmunity by this means will need to be addressed before it can be considered for use in humans.











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