Targeting cancer with cancer

16 July 2018

The natural tendency of circulating cancer cells to seek out their parent tumours, or sites of cancer spread called metastasis, can be used therapeutically to trigger tumours to kill themselves, US scientists have shown...

Cancer cells grow invasively, without recourse to tissue boundaries or the normal rules that limit the lifetime of a dividing cell. They also characteristically break away from the parent or primary tumour and establish new tumours elsewhere in the body. 

But like pigeons, cancer cells also have a homing instinct, and cells circulating in the blood stream will preferentially attempt to rejoin existing tumour masses.

This behaviour, Harvard researcher Khalid Shah realised, could be exploited as a new form of treatment in which a sample of a patient's cancer cells is harvested and the cells reprogrammed to deliver a death signal called TRAIL, which stands for TNF-related apoptosis-inducing ligand. 

Injected back into the bloodstream, the cells would make their way into the primary - and any secondary - cancer deposits where they would secrete the chemical death signals onto their neighbouring tumour cells, causing them to commit suicide. To protect the suicide-signal bearing cells from self-destruction, they are first genetically engineered in the dish to remove the chemical receptors (called DR4 and DR5) required for the TRAIL death signal to work.

For safety, the researchers also add to the modified cells a gene encoding a separate "kill switch". This can be thrown by administering a drug called ganciclovir, terminating the modified cells instantly.

The Harvard team, writing in Science Translational Medicine, have actually taken two separate approaches in developing the new treatment, which has so far been developed and tested in mice.

One approach is envisaged as an "off the peg" solution comprising pre-made modified "allogeneic" or foreign cancer cells which would be used in any recipient and injected directly into a primary cancer to help to destroy it, perhaps alongside other traditional chemotherapies. The benefit of using pre-prepared cells is the speed with which the treatment could be made available.

The other approach uses "autologous" or self cells. These are collected from a patient's own tumour and modified in the culture dish to beef up their production of the TRAIL death signal and simultaneously deactivate their own sensitivity to it. The safety kill switch is added at the same time.

In both cases the cells can be injected directly into tumours, into the cavity left behind when a tumour has been cut away, or injected into the blood stream. Mice with experimental tumours treated with the new therapy achieved double the survival times of untreated animals.

But are there not risks from exposing a cancer patient to an additional cancer burden? "Of course," says Shah. "This needs to be taken with more than a grain of salt! But where we will begin is in cancers where we have made no progress in the last 2 decades, like brain cancers that have a very poor prognosis of only 18 months survival from the time of diagnosis."

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