Personalized Cancer Treatment Edges Closer With CRISPR Trial Success

A new cancer treatment that trains the patient's own immune system to target tumor cells has been developed and successfully trialed in human cancer patients.

The therapy uses the CRISPR-Cas9 system for genetic engineering and paves the way for future advances in personalized cancer treatment.

Survival rates vary significantly between different cancer types, ranging from 98 percent for testicular cancer to just 1 percent for pancreatic cancer. On average, 67 percent of people with cancer in the U.S. will survive for at least five years after the diagnosis, and many cancers can be cured if they are detected early and treated.

However, the disease is still responsible for nearly one in six deaths worldwide, and the standard treatment is associated with numerous unpleasant side effects.

One of the main limitations of treatments today is the difficulty of specifically targeting cancer cells while avoiding healthy ones. In the last 10 years, a new class of treatments has been introduced that aims to support the immune system against cancers, rather than target the cancer cells directly. By using the body's natural defense system to attack the cancer, non-cancerous cells in the body can be left unharmed.

Scientist in lab testing samples
A file photo of a scientist testing new therapies. Immunotherapy has emerged as a new form of cancer treatment in the last 10 years. dusanpetkovic/Getty

The latest study, published in the journal Nature, details the first successful human trials using CRISPR technology to genetically engineer cells from the human immune system to recognize and destroy cancer cells.

"We are reporting on what is very likely the most complicated treatment approach ever tried in humans: a personalized gene engineered immune cell therapy using CRISPR," Antoni Ribas of the University of California, who led the study, told Newsweek.

Personalized medicine in this context involves genetically engineering the patient's own body cells. First, white blood cells that have specifically evolved to recognize the patient's cancer are isolated from the patient's blood. The genetic sequence for the receptors on these cells is then copied and inserted, using CRISPR, into other white blood cells that aren't yet able to recognize the patient's cancer.

In this way, a whole army of patient-specific immune cells can be generated that can recognize and attack the malignant cells while leaving healthy cells unscathed.

In the trial, 16 patients with metastatic solid tumors that were resistant to standard therapies received white blood cells that had been genetically engineered to recognize their own specific cancer mutations.

While only one patient showed a noticeable decrease in tumor size that could be definitively attributed to the treatment, five of the 16 showed tumor stabilization. This might not sound like much, but it marks a major step forwards in the development of future cancer treatments.

"We knew this was the first step," Ribas said. "It provides a new roadmap on how to redirect the human immune system to specifically target mutations in the patient's own cancer."

Just two of the patients displayed any significant side effects that could be attributed to the treatment, with one experiencing fevers and the other temporary confusion. Overall, though, the treatment was considered to be generally safe.

"This is a phase one trial with the goals of testing the feasibility and safety of the approach, and based on these goals it has been a successful trial."


References

Foy S. P, et al. Non-viral precision T-cell receptor replacement for personalized cell therapy, Nature, November 10 2022, doi: 10.1038/s41586-022-05531-1