A new type of immunotherapy helps immune cells "arm" themselves by releasing their own drugs to prevent exhaustion, allowing them to continue fighting cancer. In a small ongoing trial, 100% of patients achieved complete remission, and the new approach is faster and cheaper than existing immunotherapies.
The immune system remains our best weapon against cancer, but it can also be defeated by this cunning enemy. Immunotherapy is an emerging treatment approach that could help us regain the upper hand by removing immune cells from a patient's body, making them super-powerful in fighting cancer, and then returning them to the body to continue their work.
The technique has shown promise in humans, particularly against liquid cancers, but so far they have had mixed results against solid tumors. The main reason for the problem is that modified immune cells called chimeric antigen receptor (CAR) T cells can become exhausted in the stressful environment around tumors and lose their effectiveness, allowing the cancer to rebound. Currently, a major area of research is finding ways to rejuvenate CART cells using stem cells or molecules, or by blocking proteins or genes that slow down CART cells.
In the new study, EPFL scientists developed a new way to boost CAR-T cells to prevent their exhaustion. The team engineered the cells so that they excrete a molecule called interleukin-10 (IL-10), which helps them continue to proliferate and function near the tumor -- the researchers say it's like the immune cells are making their own medicine, allowing them to continue to survive in the harsh environment the tumor creates around itself.
In tests on mice, the team found that IL-10CART cells completely eliminated a range of different types of cancer, including melanoma, colon, breast and pancreatic cancer. Even if the cancer cells are later reintroduced into the animals, vigilant immune cells prevent them from establishing new tumors.
Professor Tang Li, a co-author of the study, said: "We have bioengineered a more powerful, superior immune cell that is particularly effective at targeting and destroying tumor cells, thus adding another layer to CAR-T cell therapy."
In clinical trials of the therapy, all 11 patients so far have reportedly achieved complete remission, although the trial is still ongoing.
In addition to improved efficacy, IL-10CART cellular immunotherapy also has other advantages. The number of modified cells required is smaller, only 5% of the usual dose of other immunotherapies. This significantly reduces cost (it can cost hundreds of thousands of dollars) and time (growing enough cells from a sample can take weeks or even months).
"A small amount of the patient's blood can provide enough cells to prepare CAR-T cell therapy using our technology. They can be injected back into the patient the next day. This will greatly reduce production costs, speed up production, and ultimately save more lives."
The research was published in the journal Nature Biotechnology.