In healthy individuals, the body recognizes its own proteins as “self” and so prevents the immune system from attacking its own cells. This self-protective aspect of the immune response becomes a problem, however, in cancer immunotherapy because the immune system develops self-tolerance toward the cancer cell proteins (called cancer antigens) and is unable to mount a robust immune response against them. In this issue of Nature Biotechnology (Vol. 20, No. 2, 01 Feb 02), Rong-Fu Wang and Helen Wang propose a way to get around this self-tolerance by using dendritic cells to boost an otherwise poor immune response against implanted tumors in mice.
Dendritic cells internalize various proteins, chop them up into tiny bits, and “present” them to the cells that actually carry out the cell-mediated immune response—that is, the T cells. Efforts have been made in recent years to use dendritic cells pretreated with cancer antigens as agents (called “adjuvants”) to boost a typically weak immune response. The results from these studies, though promising, have not produced complete tumor regression or therapeutic benefit. Wang and Wang suggest that this limitation possibly arises from the fact that when dendritic cells are treated with peptides from cancer antigens, they are unable to “present” these peptides efficiently for long periods of time, possibly because the antigens are not taken fully into the dendritic cells, thereby dampening the immune response.
To get around this problem, they attached a “cell-penetrating peptide” to the cancer antigen, such that the whole fusion peptide can now efficiently enter the dendritic cell and be processed and presented for prolonged periods. They show that immunization of mice with this fusion peptide results in complete protection against tumor challenge as well as inhibition of pre-existing tumors.
Their approach may be generally applicable for enhancing the efficacy of dendritic cell–based peptide vaccines against cancer and potentially many other diseases.
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