In the battle against cancer, immune cells serve as an ally, especially when they’re specifically engineered to seek out and attack the enemy. Novartis is collaborating with the University of Pennsylvania to cultivate these “special forces” for patients, developing a cell therapy called CTL019 that’s being tested in certain blood cancers.
“CTL019 has proven to be a very powerful therapeutic for a select number of cancer patients in early phase trials,” says Phil Gotwals, an executive director in oncology at the Novartis Institutes for BioMedical Research. “This gene editing technology might allow us to extend the approach to help more people.”
Currently, the experimental treatment involves harvesting T cells from a patient, re-engineering them to express a synthetic protein called a chimeric antigen receptor (CAR), and then placing them back into the same patient. The altered immune cells recognize a marker on the surface of cancer cells and destroy their target.
It seems to work well in pediatric patients with acute lymphoblastic leukemia (ALL), generating complete remissions in 36 of 39 children with the relapsed/refractory form of the disease as of late 2014. Adults with chronic lymphocytic leukemia (CLL) also potentially benefit from the treatment, though the response rate isn’t as high.
“The lower CLL response rate could be partly due to the quality of the cells coming out of the adult patients,” says Gotwals. “In some cases, they might not be good enough for therapy because they’ve been damaged by the disease.”
Ideally, the team would harvest robust T cells from healthy volunteers, re-engineer them to target cancer and give them to patients. But a patient’s immune system would likely view the donor cells as foreign and attack them. Or the donor cells might attack the host.
Gotwals and his colleagues plan to further modify the CAR T cells to avoid this scenario. They will still employ a viral vector to introduce CAR into the cells, but then they’ll turn to CRISPR for a second round of editing to make the cells less recognizable to the host’s immune system.