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Harnessing T cells may lead to significant new cancer treatments.
Modifying immune cells may offer a promising approach to target tumor mutations in mice, a recent study published in Clinical Cancer Research suggests.
The immune system has T cell receptor molecules that patrol the body, which scan the surface of cells looking for antigens.
Antigens are produced within cells and are typically derived from pathogens. They can also come from abnormal proteins that result from mutations in the cancer cells genes. If the foreign cells are recognized by the T cells, they will kill them.
Typically, the cells in the tumors are inactive, which renders them therapeutically useless as a defense mechanism during the formation of tumors.
"But it is possible to obtain fresh T cells from a patient's blood and transfer tumor-specific T cell receptors into them," said researcher Matthias Leisegang. "The transfer of the T cell receptor is carried out using genetically modified and functionally inactivated viruses that can insert their genetic material into millions of T cells. When these modified cells are infused into the patient, they are able to fight the tumor."
Researchers from the University of Chicago did an analysis on gene therapy with T cell receptors in mice. They first analyzed the genes in an individual mouse tumor, then they identified the mutation that occurred in all of the tumor regions and became an antigen.
T cells were then taken from the mouse, given a T cell receptor that could target the antigen, and then put back into the mouse. The cells were destroyed in the tumor almost entirely, but the therapy had to be used in combination with local radiation in order to eliminate the tumor in the long run.
Prior research showed the importance of animal studies to ensure the success of mutation specific therapies. This is because some mutations can seem like a perfect target for therapy after tests in cell cultures, but can end up with results that have little effect.
The researchers were able to determine which T cell targets were good and bad by using a humanized mouse model.
"This means that we have developed an animal model to test the therapeutic suitability of T cell receptors and antigens, which is an important prerequisite for clinical applications," Leisegang said.
Although the results were positive in the mice, it is not yet ready to be tested on humans. Currently, clinical tests that target antigens without mutations are ongoing.
However, this new method is complex because it is necessary for it to be individualized for each patient in order to have the best results.