Supercharging for T-cells
One way to treat some cancers is to program the patient's own T-lymphocytes against cancer cells. This is the so-called CAR-T-cell therapy, currently it is prescribed for some types of leukemia, but it is practically not effective for solid tumors, such as lung or breast cancer.
Researchers from the Massachusetts Institute of Technology have developed a way to "recharge" CAR-T cells and use them against almost any type of cancer. Group
In experiments with mice, vaccine-enhanced T-cells completely eliminated tumors in 60% of the animals. Without the vaccine, CAR-T lymphocytes did not have this ability.
Take aim at the tumor
Currently, the FDA has approved two types of CAR-T cell therapy, both for the treatment of leukemia. To do this, T cells taken from the patient's blood are reprogrammed to target a protein on the surface of B cells.
One of the reasons for the ineffectiveness of this tactic for solid tumors is that tumors usually create an immunosuppressive environment that "disarms" T-lymphocytes before they reach their target. Researchers have created a vaccine that gets into the lymph nodes and stimulates huge populations of CAR-T cells in them, making them more resistant to disconnection.
To create such a vaccine, the researchers added a so–called lipid tail to the antigens - a fat molecule capable of binding to albumin. Albumin protein circulates in the blood and moves the vaccine through the bloodstream, delivering it to the lymph nodes.
In addition to the lipid tail, the vaccine contains an antigen that stimulates CAR-T cells in the lymph nodes. An antigen can be made either directly a tumor antigen, or any molecule chosen by researchers. In the second case, CAR-T cells need to be reconstructed so that they can be activated by both tumor and arbitrary antigen.
In an experiment on mice, the researchers showed that any of the vaccines significantly enhances the T-cell response. When about 50,000 CAR-T lymphocytes were injected into mice without the vaccine, they practically did not enter the bloodstream. On the contrary, if the reinforcing vaccine was administered the day after the infusion of T cells and again a week later, CAR-T was divided until they accounted for 65% of the total population of animal T-lymphocytes two weeks after the start of therapy.
CAR-T without the vaccine did not affect tumor growth, CAR-T with subsequent administration of the vaccine eliminated tumors (glioblastoma, breast cancer, melanoma) in an average of 60% of mice.
Long-term memory
According to the authors, the "supercharging" technique promises to prevent tumor recurrence. Approximately 75 days after treatment, the researchers injected mice with tumor cells identical to those that formed the original tumor, and these cells were destroyed by the immune system. About 50 days after that, the researchers injected other tumor cells (they did not express the antigen targeted by the original CAR-T cells), but the mice were able to destroy these tumor cells as well.
In other words, as soon as CAR-T lymphocytes begin to destroy the tumor, the immune system acquires the ability to detect additional tumor antigens and generate populations of T cells that also target these antigens. The success of the technique is that T cells attack many different antigens. If CAR-T "sees" only one antigen, then the tumor is able to protect itself from an immune attack by changing this antigen with a mutation.
Most of the experiments in the study were conducted on mice, but the authors demonstrated the effectiveness of the vaccine on human cells: the vaccine with CAR antigens also stimulates CAR-T lymphocytes. So, this approach can work for people as well.
There are no obstacles to testing the method in patients, this may happen in the next 1-2 years.
Article by L. Mart al. Enhanced CAR–T cell activity against solid tumors by vaccine boosting through the chimeric receptor is published in the journal Science.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on MIT materials: New vaccine strategy boosts T-cell therapy.