Human CRISPR trial heralds Longevity success

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Click the globe for translations.

Trial finds not only that gene-edited immune cells are safe, but that they survive and thrive after being placed into patients suffering from advanced cancer. “Is it safe and feasible? I think that’s what we demonstrated.”

Researchers have demonstrated that CRISPR-edited cells removed from patients months after treatment were able to kill cancer even in a lab setting.

Longevity.Technology: This is exciting news for cancer therapy. The first human CRISPR trial of its kind used three participants who had tumours that had failed to respond to other treatments and edited three genes, rather than just single ones, meaning that the door to treating diseases and conditions previously thought to be untreatable has been opened a little wider, since they are often the expression of more than one gene.

In this trial, the team from the Perelman School of Medicine at the University of Pennsylvania and Penn’s Abramson Cancer Center removed immune cells from three people who had tumours with the same protein on their surface. Then a virus was used to add a gene that stimulated the immune cells to target this protein.

The researchers deleted three genes, using CRISPR/Cas9 editing to remove them. The first two edits removed the natural receptors from T cells, meaning they could be reprogrammed to express a synthetic T cell receptor. This enabled these altered cells to seek out, find and destroy cancerous tumours.

CRISPR explainer from the University of Pennsylvania

The third edit removed PD-1, the so-called programmed cell death protein 1; PD-1 down-regulates the body’s immune system, protecting it from autoimmune diseases, but with the downside of sometimes preventing the immune system from killing cancer cells by blocking T cells from carrying out this function. After a period of six weeks culturing and editing the cells, they were put back in the patients, where they were found to have survived for at least 9 months.

Dr Carl June, senior author of the study said: “Our data from the first three patients enrolled in this clinical trial demonstrate two important things that, to our knowledge, no one has ever shown before. First, we can successfully perform multiple edits with precision during manufacturing, with the resulting cells surviving longer in the human body than any previously published data have shown. Second, thus far, these cells have shown a sustained ability to attack and kill tumors [1].”


… two potential dangers – that unintended changes might occur and cause cancer or that the CRISPR protein might trigger an immune reaction – were not evidenced …


 

The trial was intended to show that safety of the edited cells, rather than their efficacy, but the two potential dangers – that unintended changes might occur and cause cancer or that the CRISPR protein might trigger an immune reaction – were not evidenced. The next stage will to be to test and explore the benefits of cell-based therapies.

That gene editing research is proceeding with with such evident checks and balances is likely to be of comfort to both the scientific community and the general public, who were shocked by some unorthodox CRISPR experimentation in China. CRISPR isn’t the only gene editing tool available, either, as Prime Editing is thought by some to be more accurate and more versatile.

Speaking of this human trial, team member Edward Stadtmauer at the University of Pennsylvania said: “Is it safe and feasible? I think that’s what we demonstrated.” He went on to consider the future of gene editing therapy: “The possibilities are limitless based on our imagination and scientific focus [2].”

[1] https://bit.ly/3buok7d
[2] https://bit.ly/2OOcbjH

Eleanor Garth
Deputy Editor Now a science and medicine journalist, Eleanor worked as a consultant for university spin-out companies and provided research support at Imperial College London and various London hospitals in a former life.

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