May 22, 2019 06:00:00

What is the next step of CAR-T therapy that brings T cells to a 'killer' to eradicate cancer?

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qimono

CAR-T cell therapy for treating blood cancers such as leukemia using genetically engineered T cells has been highly effective since it was approved by the US Food and Drug Administration (FDA) in 2017. On the other hand, the effect of CAR-T cell therapy on solid tumors is said to be still limited. Rafael Amado, who is trying a new approach to CAR-T cell therapy for solid tumors, explains the next step in CAR-T cell therapy.

The Next Wave of Immuno-Oncology-Scientific American Blog Network
https://blogs.scientificamerican.com/observations/the-next-wave-of-immmuno-oncology/

CAR-T that leads to cancer cell death by genetically engineering T cells in the body and culturing them outside the body, teaching them as 'killer T cells' that attack cancer, proliferating, activating and then returning them to the body You can read about cell therapy from the following articles.

What is 'CAR-T therapy' that teaches genetically killed immune cells to 'kill' and leads to the death of cancer cells? -GIGAZINE

The key to successful CAR-T cell therapy is the presence of antibody fragments that bind to a protein called the 'CD19 antibody'. Antibody fragments are linked to stimulatory and signal molecules that are generated when the antibody binds to the antigen CD19, which allows T cells to recognize cancer specific antigens and kill cancer cells. It will be possible.

On the other hand, the effect of CAR-T cell therapy on solid tumors has so far been considered poor. The reason is that although CAR-T cells need to accumulate and proliferate in the tumor area to exert therapeutic effects on solid tumors, such techniques have not been established. And why CAR-T cells do not collect around solid tumors, many cancer-specific antigens are expressed intracellularly, and cancer-specific antigens expressed on cell surfaces that can be recognized by CAR-T cells Is limited.

One approach to solving this problem is to target proteins inside the tumor rather than on the tumor surface. Some cancer cells expressed in the cell bind to major histocompatibility complex (MHC) on the surface of cancer cells as antigenic peptides. Since MHC plays a role in causing T cells to recognize allies and enemies, it is possible to target solid tumors if T cells recognize peptide and MHC on the tumor surface.

T cells are 'investigators' and 'killers' in the immune system. T cells have T cell receptors (TCRs) , and around the body, they use TCRs to find and bind to viral or bacterial infected peptides.

However, unlike proteins of foreign substances, proteins of cancer cells are very similar to proteins originally possessed by humans. For this reason, it is difficult to efficiently target a tumor using the TCR that the body originally has.

The approach taken there is to enhance the natural TCR. Engineered in such a way as to optimize the binding between TCR and peptide, the receptor can more easily recognize cancer cell proteins. By engineering TCRs back into the human body outside the human body, you will be able to find and kill more cancer cells in patients than natural TCRs.

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The company Adaptimmune, for whom Amado works, is one of the companies that is trying to engineer the TCR as described above. Adaptimmune has developed a method to target a protein called NY-ESO in 'SPEAR T cell therapy' for engineering TCR, which has been shown to be effective in two types of sarcomas. In addition, it is said that Adaptimmune is conducting research to further enhance the ability of T cells to target tumors, aiming at a longer-term anti-tumor response.

There are many other companies looking for ways to eradicate metastatic cancer. As the T-cell researchers have won the 2018 Nobel Prize in Physiology and Medicine, the field has made significant strides. As researchers continue to unravel the complex interactions of cancer and anti-cancer immunity, the potential for the future is promising, says Amado.