A new clinical trial published in the journal Science has found that genetically-modified immune cells could persist, thrive and even function months after they are infused in patients with cancer.
Researchers from the Abramson Cancer Center of the University of Pennsylvania found that cells removed from patients and edited in the lab setting were able to kill tumor cells months after their infusion.
This is the first clinical trial in the United States to test the gene-editing approach in humans. The immune cells were edited using CRISPR/Cas9 technology.
Senior study author Dr. Carl June 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,” added Dr. June.
The new findings are the groundbreaking discovery in Penn’s history in the field of cellular and gene therapy, including Kymriah (tisagenlecleucel), the first FDA-approved CAR-T cell therapy for blood cancer in children and adults.
The approach of this trial was based on CAR-T cell therapy, in which the patients’ immune cells genetically modified to combat cancer. However, there are a few differences between CAR-T and the approach used in this trial. The researchers used CRISPR/Cas9 editing to remove three genes in the immune cells.
Dr. June explained the new analysis “has confirmed that the manufactured cells contained all three edits, providing proof of concept for this approach.”
“This is the first confirmation of the ability of CRISPR/Cas9 technology to target multiple genes at the same time in humans and illustrates the potential of this technology to treat many diseases that were previously not able to be treated or cured,” Dr. June added.
After genetically-editing the immune cells in the lab setting, three patients who were involved in the trial received the cells in a single infusion after a short course of chemotherapy.
The researchers analyzed their blood samples of the three patients and found that the CRISPR-edited T cells persisted and functioned for months.
In the United States, CRISPR/Cas9 technology has not previously been tested in humans. Penn researchers were the first to do so. They said their findings would open the door for larger studies and extend the approach of the new technology to fight cancer.
