CAR-T cells created inside mice with human T cells in the US — ScienceDaily
Researchers at the University of California, San Francisco, USA, have developed a method for creating CAR-T cells directly inside the body. The experiments were conducted in mice with a humanized immune system, using human T cells. The new approach was used against aggressive leukemia, multiple myeloma, and a solid sarcoma tumor, ScienceDaily reports.
CAR-T therapy involves the genetic modification of T cells, which are immune system cells. After their DNA is altered, they produce chimeric antigen receptors that recognize certain proteins on cancer cells and trigger their destruction. The conventional process requires cells to be collected from a patient, sent to a specialized facility for modification, and then returned for administration. This can take weeks and cost between $400,000 and $500,000.
Two particles for DNA editing
The new system uses two particles that deliver the CRISPR-Cas9 genome-editing tools and DNA containing instructions for creating a CAR to T cells. The surface of one of the particles was coated with antibodies to the CD3 protein, which is found only on the surface of T cells. This is intended to direct the system specifically to these cells.
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The second particle delivers DNA containing instructions for producing a CAR, as well as information for inserting it into a specific site in the T-cell genome. This site has a molecular switch that is active only in T cells. According to the researchers, this is the first time a large DNA fragment has been inserted into a precise location in the genome of human T cells without first removing them from the body.
Results in mouse experiments
After a single administration of the two-component treatment, all detectable signs of cancer disappeared within two weeks in nearly all mice with aggressive leukemia. In some organs, the newly created CAR-T cells accounted for up to 40% of the immune-cell population. The treatment also eliminated cancer from the bone marrow and spleen.
According to the authors, the same strategy was effective against multiple myeloma and a solid sarcoma. The researchers also noted that T cells reprogrammed inside the body performed better than comparable cells created in a laboratory. At the same time, the technology is not yet ready for use in humans: it needs to be scaled up, and its safety and efficacy must be tested in clinical trials. For the platform's further clinical development, the scientists founded Azalea Therapeutics.
