An immune therapy designed to treat any type of blood cancer has been successfully administered to mice and, according to the scientists who developed it, could begin testing in patients within two years.
The advance is based on editing cells of the immune system so that they recognize and attack the CD45 protein. This protein is found in all white blood cells and therefore also in leukemia and lymphoma cells.
Since the blood stem cells found in the bone marrow also have the CD45 protein, treatment requires a marrow transplant with cells modified so that they are not attacked by the immune system itself.
The new immunotherapy "is presented as an option for patients who do not respond to current treatments and for whom a bone marrow transplant may be indicated," says Manel Juan, head of the immunology service at Hospital Clínic in Barcelona, who has not participated. in this project but is investigating a similar treatment.
"It is an extremely promising strategy," says Ignacio Melero, an immunologist at the Clínica Universidad de Navarra and the CIMA research center. “In principle it can be effective in practically all hematological malignancies; It's very hopeful."
The research is being carried out at the Center for Cellular Immunotherapies at the University of Pennsylvania (USA), directed by Carl June. This doctor against all odds cured a six-year-old girl of leukemia in 2012, proving that CAR-T therapies can be effective for cancers for which there are no other treatment options.
Since then CAR-T therapies have saved thousands of patients with blood cancers around the world. These therapies consist of modifying patients' T lymphocytes in the laboratory (a type of immune cell capable of destroying cancer cells) and injecting them again so that they recognize and attack leukemia and lymphoma proteins.
However, not all blood cancers can be successfully targeted with current CAR-T therapies. To overcome this limitation, the team from the University of Pennsylvania has developed "a universal immunotherapy for blood cancers", as defined in the journal Science Translational Medicine , where they are presenting their results today.
It is also a CAR-T therapy, but with the novelty that the immune cells direct their attack against the CD45 protein, which is common to all leukemia and lymphoma cells. Until now, attacking CD45 has been considered infeasible because it is also found on healthy cells of the immune system.
In the key research breakthrough, the University of Pennsylvania team has devised a way for the immune system to attack cancer cells without self-destructing.
It has done so by introducing a small modification in the CD45 protein of the cells that will be used for bone marrow transplantation. The change is enough to stop CD45-targeted CAR-T cells from attacking the marrow itself, but it does not stop the marrow from functioning normally and generating competent blood cells.
“We think this concept could be used for any blood cancer, including various types of lymphoma, leukemia, and multiple myeloma,” Saar Gill, who co-led the research with Carl June, says by email.
The same treatment could cure HIV infection in any carrier of the virus who has to undergo a bone marrow transplant for another reason, the researchers note in Science Translational Medicine.
In contrast, it is not expected to be useful against solid tumors, since they do not usually have the CD45 protein, reports Saar Gill.
The treatment has been tested in mice that were inoculated with human cancer cells and developed acute myeloid leukemia. A single injection of CAR-T lymphocytes directed against the CD45 protein was enough to achieve a complete cure. Three months later, the mice were inoculated again with leukemia cells obtained from patients. But on this second occasion they did not get sick, which indicates that their immune system remained active to avoid relapses.
Additional experiments with cells from patients indicate that CAR-T cells directed against the CD45 protein also kill cells from other types of leukemia and lymphomas.
The researchers plan to conduct trials in non-human primates in the coming months before beginning to administer the therapy to people. If the results are positive as expected, reports Saar Gill, "we think that within two years we can be in the clinic."
