Fighting Cancer with Cancer

17 July 2018

Interview with 

Khalid Shah, Harvard Medical School

CANCER-HEADLINE

Headline about cancer

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If someone told you that they wanted to treat your cancer by injecting you with more cancer cells, you’d be right to be sceptical. But that’s exactly what researchers at Harvard Medical School are doing, because they’re exploiting a natural tendency of cancer cells to home back in on their parent cancer deposits, or join into sites of cancer spread, called metastases. Khalid Shah has developed a way to genetically engineer harvested tumour cells to make them churn out therapeutic “death signals” so that when the cells are reinjected into the body, they seek out tumours and trigger nearby cancer cells to kill themselves. As a safeguard, the modified cancer cells have an in-built “kill switch” so they can be terminated once their job is done, as Chris Smith found out.

Khalid - One of the major hurdles for advance stage cancer is that they're localised but they also move from one organ to another. They also can move from the other organ back to the same place where they originated and we can sort of repurpose the tumour cell homing properties for delivery of targeted therapeutics to the primary tumour cells.

Chris - So are you saying then clearly that what you can do is take a cell from a tumor that wants to get back to its home tumor, and do the equivalent of say brainwashing a terrorist and releasing that terrorist back onto the street, to lead you back to where he came from or she came from?

Khalid - Yes, you're right. So we can actually tame a cancer cell. We actually re-engineered it to produce therapeutics and then kill the original tumour cell. How on earth did you do that. So we used two properties, let's assume you have two cancer patients; one has a cancer resistant to a particular drug, and one has cancer sensitive to a particular drug.

What we did is we took the tumour cell that is resistant to a particular drug and engineered it to release therapeutics that can kill the tumour that is sensitive to that drug. The second approach is that we took the patient's own cells, which sends it to a particular therapy and we gene-edited its surface receptors to make them resistant first, then engineered them with therapeutics and a “killswitch”. With the therapeutic, we can kill the original cell and with the killswitch we can kill the re-engineered cell.

Chris - This is neat. Basically you're using the natural homing behaviour of cancer cells to get into tumors that have spawned cancer cells that are trying to spread around the body. When they go back into the tumor, they detonate an explosion that's going to kill the parent tumor but you've also put a safeguard in there which is that you can kill the cells you’re putting back in because you've got this additional, as your dubbing it, “kill switch” engineered in there.

Khalid - Yes. The beauty of the killswitch is also that it can be imaged by PET imaging so we can actually track the re-engineered cell in the body.

Chris - How do you endow the cancer cell with the ability to kill the parent cancer but itself not be killed by the toxic cargo it's carrying?

Khalid - Cancer cells have these unique signatures on their surface that make them cancer cells. One of them is death receptors on the surface of the tumor cell. What we did with gene editing technique is that we knocked out the receptors on the surface of the tumour cell. So it's not killed by therapeutic it's producing.

Chris - These cells that you infuse, can they access all areas? Can they both go to the parent tumor, that spawned the person’s disease and it's spread, and could they potentially also therefore access the metastases where it spread to?

Khalid - Yes, we have tested this in mice and we've shown that if you inject them into the primary tumour site they can eradicate that primary tumor cells. We also injected them systematically in one of the arteries that leads to the brain and we can show that they can track and can kill metastatic tumour cells in the brain as well.

Chris - It might worry some people though the prospect that you're injecting people with not just a genetically modified cell, but a genetically modified cancer cell. Are there no risks associated with doing this?

Khalid - Absolutely. I don't think it will be taken without a grain of salt because you're putting cancer cells back into the patient. I think the first indication would be going into the tumors cells which have an unmet need where we haven't done anything for last two decades. One of the prominent tumours is the brain tumour where the survival is between 12 to 18 months post diagnosis. So yes, if we can assure people that we have the engineer tumor cells under control and we can kill them any time, I think the first indication would be in the most unmet need tumours.

Chris - And is there no risk that the infused modified cells could go rogue and undo the killswitch you've engineered into them and then you've actually given that person an even worse prognosis

Khalid - No, because we use anti-viral vectors that integrate into the genome of the cell. So whatever we have engineered the gene that we have engineered is incorporated into the genome and the cells so there's very low chance of these cells going rogue and leaving the gene out.

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