It's all in the presentation
Harnessing the body’s own immune system to fight cancers is elegantly simple in theory but has proven difficult in practice. Two new techniques may help bring researchers a step closer by overcoming one of the main teething problems—getting cancer-associated proteins (antigens) "seen" by the immune system (Nature Biotechnology, Vol. 18, Issue 12, 01 Dec 2000).
The major players here are the dendritic cells, which carry out the job of presenting the antigen to the immune system. This is an essential step in triggering an immune response against the foreign protein and thereby the cancer. However, dendritic cells have proven difficult to manipulate and coaxing them to adopt the cancer antigen can be tricky.
Andrew Mountain’s research team has got around this problem by delivering DNA encoding the cancer-associated antigen to dendritic cells. First, they mixed the DNA with a peptide that condenses it and encourages its uptake and exposed dendritic cells to the mixture. When the dendritic cells that had been modified were injected into mice, the researchers found an immune reaction that slows the growth of tumours.
Independently, Damir Vidovic and his colleagues have developed a way of encouraging antigen-presenting cells, including dendritic cells, to take up antigen directly. Because of similar, and therefore repulsive, charges, antigens do not naturally penetrate the cell membrane. Vidovic and his team have overcome this problem by linking two discrete peptides to the antigen. One peptide neutralizes the antigen’s charge, easing its passage across the membrane. The other frees the antigen inside the cell, allowing it to be more readily presented by the cell and evoking a strong immune response. The next stage will be to test whether these transformed cells can also halt tumour growth in mice.
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(C) Nature Biotechnology press release.
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