TAILOR-MADE antibodies can be used to fight certain forms of cancer,
according to a team of German researchers. Michael Pfreundschuh and his
colleagues at Saarland University in Homburg, Germany, have designed antibodies
to attract immune T cells to the site of a tumour and induce them to kill
it.
Natural antibody molecules have two binding sites, which both bind to a
single type of antigen鈥攁 chemical marker on the surface of a cell. Now the
researchers have made antibodies that are bispecific鈥攖hey bind to two
different antigens. They reasoned that if an antibody binds to antigens on two
different types of cell鈥擳 cells and tumour cells鈥攖hen the molecule
would act as a bridge to hold the cells together.
But simply holding immune T cells and tumour cells together is not enough to
induce the T cells to kill the tumour cells. The T cells have to be activated,
and this only happens when receptor molecules on the T cell engage their
counterparts on the tumour cell. The researchers mimicked this by stimulating
the receptors with one of the antibody鈥檚 binding sites.
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Pfreundschuh and his team tested a combination of two bispecific antibodies
to treat Hodgkin鈥檚 tumour of the lymph glands. One binding site of each antibody
attaches to CD30, an antigen on the surface of Hodgkin鈥檚 tumour cells. The other
binds to either CD3 or CD28, receptors which together activate the T cell.
The team used mice with a genetic defect in their immune system, which means
they can be injected with human cells without rejecting them. The mice injected
with Hodgkin鈥檚 tumour cells alone all died in around 40 days. In contrast, when
the researchers injected the antibodies and human T cells into mice with
widespread tumours they were all completely cured.
鈥淭his is a very good model because it uses human cells and so it is as close
to the human situation as we can get,鈥� says Pfreundschuh.
They showed that T cells taken from patients with Hodgkin鈥檚 tumour worked as
well as T cells from healthy people. So Pfreundschuh speculates that the tumour
cells in cancer patients would be killed.
However, the mice were only cured if the treatment was given within seven
days of the injection of tumour cells. If it was left any later, then the tumour
always outstripped the treatment in the end, although the treated mice still
survived longer than the untreated ones. 鈥淭he timing is critical,鈥� says
Pfreundschuh. 鈥淚t is a reflection of tumour load. It is difficult to relate this
to the clinical situation, but I speculate that this treatment will be
蝉耻肠肠别蝉蝉蹿耻濒.鈥�
鈥淎 cure in a mouse does not necessarily translate into a cure in humans,鈥�
says Peter Beverley, scientific head of The Edward Jenner Institute for Vaccine
Research near Oxford. 鈥淢y worry is that the antibodies won鈥檛 get to the tumour
cells, so I am rather sceptical as to whether every last cell will be killed.
However, if this treatment is given after standard treatment has substantially
reduced the tumour load then I would be cautiously optimistic鈥�.
Pfreundschuh and his colleagues have published their findings in
Blood (vol 87, p 2930).
