Novel therapy minimizes brain injury caused by CAR T cell therapies

Researchers demonstrated the efficacy of a novel treatment for the treatment of controlled acute myelogenous leukemia (CML) with the use of a novel CAR T cell therapy. Using this new therapy, normal brain blood vessels in mice were enlarged without the side effects of chemotherapy and proven to be completely protected from apoptosis induced by CRISPR-Cas9-Cas9.

The study, published in Nature Microbiology, was led by Dr. Tobias Eckle, Head of the Department of Veterinary Medicine at the University Hospital Bonn and his associates. Dr. Eckle and his team have reviewed nine cases of CML, which is an extremely aggressive type of blood cancer caused by the chronic growth of white blood cells. The CML gene is found in humans and was discovered by means of CRISPR-Cas9 genome editing. Currently patients are treated with infusions of fetal blood containing antibodies that target the receptor involved in this response, which is capable of regulating the amount of tumor cells destroyed and enabling them to control blood pressure to a very high level. “In this research we have succeeded in modifying a CAR T cell for use in treating patients with targeted CAR T cell therapy,” said Dr. Eckle.

Treatment with CAR T cells was described in the study conducted at the University Hospital Bonn and respected medical centers in the Netherlands. The first patient lived close to retirements due to his advanced cancer. The treatment was successfully carried out in September 2018 at the medical centers. Two patients were cured of the disease after treatment with CAR T cells. “It is very striking to note that our CAR T cells appeared to have quite little harmful side-effects. This led us to conclude that this treatment appears to be actually quite successful,” added the researcher.

Cytotoxic lymphocytes.

Acute lymphoblastic leukodystrophy, which is also commonly treated, is a major complication caused by a high level of white blood cells. In the laboratory of Dr. Eckle, it was discovered that the brain, particularly the choroid plexus, undergoes a transformation because white blood cells no longer respond to the direct effect of the immune system. “The cells there line the spaces between nerve fibers on the choroid plexus and bud out as dividing cells. Exactly what this means and why it occurs is not known yet. Perhaps the cells eliminate them leaving only the tumor cells. We speculate that at some point the white blood cells are eliminated,” explains the researcher.

As a preventative measure these same white blood cells are also exposed to the patient’s immune system. In the therapy, these cells are stimulated to remain in the choroid partition so that these sensitive cells cannot be activated, ultimately preventing in any case the spread of cancer. “Our study indicates that T cells removed from a patient before the treatment can also safely remain in their place and not be activated. As a consequence these cells leave the brain presenting a natural defense against any uncontrolled tumor growth. Because the patient is able to live longer without the risk of relapse, preventing relapse is a tangible benefit in our view,” concludes the researcher.