Those living with cancer may soon be eligible for the most bespoke treatment to date.
New research has the potential to revolutionize the battle against cancer by “editing” patients’ own cells to fight their unique disease profile.
As part of a clinical trial, published in the medical journal Nature on Thursday, scientists used CRISPR technology to direct immune cells to attack mutated proteins that help grow cancerous tumors, while avoiding harm to healthy, non-cancerous tissue.
“This is a leap forward in developing a personalized treatment for cancer, where the isolation of immune receptors that specifically recognize mutations in the patient’s own cancer are used to treat the cancer” said study co-author Dr. Antoni Ribas, a cancer researcher and physician at the University of California, Los Angeles, in a statement by the school.
The process also improves the efficacy of conventional immunotherapy administered by doctors, which encourages a person’s own immune system to fight cancer.
The CRISPR technique has previously been used to remove specific genes from the body that would clear the path for the immune system to fight disease and deformities. CRISPR [Clustered Regularly Interspaced Short Palindromic Repeats] refers to a group of DNA sequences that act as genetic gatekeepers. In recent years, scientists have learned how to use CRISPR-associated proteins [Cas] to cut out undesirable strands of DNA and literally edit a human’s genes.
The new study uses CRISPR to develop an even more complex method, which involves removing a patient’s cells, making modifications and reinserting them back into the body — armed with new and improved instructions on how to fight specific cancers.
“It is probably the most complicated therapy ever attempted in the clinic,” Ribas told Nature in a report tied to their study. “We’re trying to make an army out of a patient’s own T cells.”
Ribas worked alongside James Heath, Ph.D., president of the Institute for Systems Biology in Seattle, and Nobel Laureate David Baltimore, Ph.D., emeritus professor at Caltech and a member of the UCLA Jonsson Comprehensive Cancer Center as well as PACT Pharma.
Their team started out by sequencing DNA in blood and tumor biopsies from each of the 16 patients involved in the trial, looking out for mutations that appear in tumors only while ignoring those that also appear in the blood. This data was fed to an algorithm that suggested which of these mutations are likely to trigger a response from T cells, an immune defender that spots invader cells — and eliminates them.
Unfortunately, the immune system on its own doesn’t have a great record of beating cancer.
Using predictions from the algorithm, researchers then engineered T cell receptor proteins— tailoring them specifically to each patient — that would recognize the mutations that went on to cause tumors. Then they delivered those specially designed receptors to each of their patients’ T cells via CRISPR — leaving their immune system better equipped with tools to locate and destroy cancer.
The cohort of 16 patients showed a variety of cancers, all of which were “solid” types, meaning their tumors don’t contain any liquid or cysts.
One month after the trial, five of the participants were stable, meaning their tumors had not grown. Their success may seem small, but researchers said they’re just getting started. “We just need to hit it stronger the next time,” Ribas told Nature.
Hannah Sparks, Emily Lefroy