Study examining how CAR T immunotherapy could be used to treat solid tumors

A study recently published in the journal Science showed how CAR T immunotherapy could be used to treat hard tumors as well as leukemias. CAR T cell programming opens pathways for the implementation of cell therapies, for example, future breast cancer or ovarian cancer.

In cancer immunotherapy, cells in the patient’s own immune system are activated to attack cancer cells. CAR T cell therapy has been one of the most important recent advances in cancer-targeted immunotherapies.

In CAR T cell therapy, T cells are removed from the patient for genetic modification: a chimney antigen receptor (CAR) is transported into the cells using a viral vector, aiding T cells to better identify and kill cancer cells. When the antigen receptor cells identify the desired surface structure in the patient’s cells, they begin to proliferate and kill the target cells.

CAR T cell therapy was introduced to Finland in 2018, and the treatment form was used to support patients suffering from leukemia and lymphomas.

To date, it has been difficult to apply CAR T cell therapy to solid tumors: it is difficult to focus on the treatment at just the eardrum when the type of cancer is not associated with a specific surface structure. bith. In many types of cancer, there is an abundance of specific proteins on the surface of the tumor, but because the protein also appears in low numbers in normal print, CAR T cell therapy cannot differentiate between protein levels. target. That is why genetically modified cells rapidly invade healthy cells and organs, which can cause the lethal side effects associated with the treatment.

A study recently published in the Science a journal has found a solution for applying CAR T cell therapy to hard tumors as well: through collaboration, American and Finnish researchers identified a new way to program CAR T cells to kill only cancer cells, which leaving alone healthy cells that have the same protein mark as cancer cells.

New technology based on ultrasensitive identification of HER2 cells, further study ongoing

HER2 is a protein that is common among others, breast cancer, ovarian cancer and abdominal cancers. The protein can also appear in large numbers on the surface of tumor cells, because, as a result of gene proliferation, HER2 expression can multiply in tumors.

A new CAR T cell engineering technique developed by the researchers is based on a two-step identification process of HER2 positive cells. Thanks to the engineering, the researchers were able to produce a response where CAR T cells only kill the cancer cells in a cancerous tumor.

Our solution requires prior identification of the surface structures associated with the cancer. When the initial recognition ability that stimulates CAR buildup is modified to require a binding relationship that is different from the relationship that CAR uses to direct the killing of these cells, a highly accurate ability to differentiate between cells based on the level of target protein on their surface can be programmed in this two-step ‘cycle’ that controls the activity of killer T cells. “

Kalle Saksela, Professor of Virology, University of Helsinki

Further studies on the use of this method are already underway. Postdoctoral researcher Anna Mäkelä, who works at Professor Saksela’s laboratory, is coordinating a project funded by the Finnish Academy examining the use of CAR T cell therapy on different types of cancer and the surface structures aca.

“We are very excited about these results, and are currently developing the method that could be used to treat ovarian cancer. As the work progresses, the goal is to use itself and build the target molecules of CAR buildup even more extensively into solid malignant tumors.Our goal is to develop ‘multi-tumor missiles’, which will make it difficult for cancer cells to fight off development, “Mäkelä says.

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Magazine Reference:

Hernandez-Lopez, RA, et al. (2021) T cell circuits sensing antigen density with ultrasensitive threshold. Science. doi.org/10.1126/science.abc1855.

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