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CRISPR technology alters immune cells to fight cancer

Researchers at the University of California, Los Angeles, have combined the use of CRISPR gene therapy with engineered immune cells for cancer treatment. The clinical trial, the results of which have been published in Nature, is the first of its kind. Described by author Antoni Ribas as “the most complicated therapy ever attempted in the clinic,” the work paves the way for personalised cancer therapies.

Engineering a solution

Every cancer is different, harbouring unique mutations which aid in the growth and progression of disease. The human immune system is equipped with T cells to help fight these rogue cells whilst leaving healthy ones intact. These cancer-fighting weapons have receptors to recognise specific mutations and can recruit other immune system components to kill anything that looks out of place.

Despite this impressive mechanism, if cancer cells are not dealt with quickly enough or develop immune-evasive mutations, the immune system cannot keep up, leaving the disease to spiral out of control.

To combat this, researchers have previously developed what are known as chimeric antigen receptor (CAR) T Cells – T cells which have been removed from a patient, genetically engineered to produce cancer-recognising receptors and multiplied by millions in a lab before being inserted back into the body via a blood transfusion. This produces an immune response against the tumour far greater than the body could produce on its own. This personalised treatment is currently only used in a limited number of cancers due to its complexity and price.  

Cut and paste

Engineering of T cells has so far relied on the use of viral vectors, but the need to personalise a vector for each patient is unrealistic. This has led to calls for a new mechanism for editing T cells, and the team chose to investigate the use of CRISPR technology for this task.

This mechanism acts like scissors and glue – CRISPR is used to “cut” unwanted sections of DNA out of a cell, and the nuclease-based technology can then “paste” a new sequence in its place. In this clinical trial, the team identified specific cancer-causing mutations in each tumour and retrieved T cells from the patients, using CRISPR to remove the genes that produce the naturally occurring receptors and replace them with the blueprints to recognise the unwanted cancer cells.

Following reinsertion into the patients’ bloodstreams, five of the sixteen patients involved in the trial showed no further disease progression a month after treatment, with two of these individual’s tumours in fact shrinking following the therapy.

A bright future for personalised medicine

Although eleven patients saw further disease progression in the weeks following the treatment, the team were keen to stress that this could be due to the cautious approach they took by only exposing patients to small amounts of engineered cells. Now that more is known about the safety of the treatment, with only two patients suffering from unexpected side effects, Ribas stated they “need to hit it stronger next time.”

The work proves that the use of CRISPR technology to engineer cancer-fighting immune cells is effective and safe, and lays the groundwork for creating more efficient and precise therapies. Despite the limitations of the study, the lessons from this clinical trial can inform future research into personalised cancer therapies. When speaking of the treatment’s potential, cancer researcher Joseph Fraietta remarked that “the technology will get better and better.”