Science: Major development of CAR-T cells that recognize the expression level of protein antigens on the surface of cancer cells, which is expected to be used in the treatment of solid tumors

March 24, 2021 //---In cancer immunotherapy, cells in the patient's own immune system are activated to attack cancer cells.
CAR-T cell therapy is one of the most important developments in recent immunotherapy against cancer.

In CAR-T cell therapy, T cells are extracted from patients for genetic modification: using viral vectors to deliver chimeric antigen receptors (CAR) to T cells to form CAR-T cells to better recognize and kill cancer cell.
When CAR-T cells recognize the desired surface structure in the patient's cells, they begin to proliferate and kill the target cell.
CAR-T cell therapy was introduced to Finland in 2018, and it has been used to treat leukemia and lymphoma patients.

So far, the application of CAR-T cell therapy in solid tumors is difficult: when there is no correspondence between the cancer type and any specific surface structure, it is difficult to treat the tumor only.
In many cancer types, there are a large number of specific proteins on the tumor surface, but the protein also has a low level in normal tissues.
Importantly, CAR-T cell therapy cannot distinguish the expression level of the same target protein in different cells.
This is why conventional genetically modified CAR-T cells will quickly attack healthy cells and organs, leading to treatment-related fatal adverse reactions.

In a new study, researchers from the University of California, San Francisco and the University of Helsinki in Finland found a solution for CAR-T cells for the treatment of solid tumors: they discovered a new kind of anti-CAR-T cell The method of programming allows them to kill only cancer cells, while letting go of healthy cells that have the same protein markers as cancer cells.

This new technology based on ultra-sensitive identification of HER2 cells is under further study

HER2 is a characteristic protein of breast cancer, ovarian cancer and abdominal cancer.
The protein can also appear on the surface of tumor cells in large amounts, because as a result of gene amplification, the expression of HER2 can increase exponentially in tumors.

A new CAR-T cell engineering technology developed by these researchers is based on a two-step identification process for HER2-positive cells.
Thanks to this engineering technology, they can make CAR-T cells kill only cancer cells in cancer tissues.

The co-author of the paper and Professor of Virology at the University of Helsinki, Kalle Saksela, said, “Our solution requires preliminary identification of cancer-related surface structures.
When adjusting the initial recognition ability for CAR construction to the need for CAR to guide the killing of target cells With different binding affinities, a very accurate ability to distinguish different cells based on the number of target proteins on the cell surface can be programmed in a two-step positive feedback loop that controls killer T cells.
"

Further application research of this technology is already in progress.
Anna Mäkelä, a postdoctoral researcher in the Saksela laboratory, is coordinating a project funded by the Finnish Academy of Sciences to study the application of CAR-T cell therapy on various cancer types and their surface structures.

Mäkelä said, "We are very excited about these results, and we are currently developing this technology so that it can be used to treat ovarian cancer.
As this research progresses, our goal is to build the technology itself and CAR It is more widely used in malignant solid tumors.
Our goal is to develop a "multi-warhead missile" that makes it difficult for cancer cells to develop resistance.
" (Bioon.
com)

Reference: Rogelio A.