Anti-cancer CAR-T therapy reengineers T cells to kill tumours — and researchers are expanding the limited types of cancer it can target

Subject: Science and Technology

Context-

Researchers have been developing a novel type of therapy that directly gives patients a new set of T cells engineered to attack tumours: chimeric antigen receptor T cells, or CAR-T cells for short.

What are T cells?

T cells are a type of white blood cell.
Also called T lymphocyte and thymocyte.
T cells are part of the immune system and develop from stem cells in the bone marrow. They help protect the body from infection and may help fight cancer.

What is CAR-T cell therapy and how does it work?

CAR-T cell therapy is a treatment to cure several types of cancer including lymphoma and multiple myeloma.
It starts with isolating a patient’s T cells from a sample of their blood.
These T cells are genetically engineered to produce a chimeric antigen receptor or CAR.
- CARs are synthetic receptors specifically designed to redirect T cells from their usual targets to recognize and kill the tumour cells.
On the outside of a CAR is a binder that allows the T cell to stick to tumour cells.
Binding to a tumour cell activates the engineered T cell to kill and produce inflammatory cytokines proteins that support T cell growth and function and boost their cancer-killing abilities.
These CAR-T cells are then stimulated to divide into large numbers over seven to 10 days, and then given back to the patient via infusion.

For which type of cancers the therapy is effective?

It’s already being used to treat lymphoma and multiple myeloma.
However, it is not effective against solid tumours.
- Unlike cancers that begin in the blood, these types of cancers grow into a solid mass (For e.g.KIdney or Pancreas) that produces a microenvironment of molecules, cells and structures that prevent T cells from entering into the tumour and triggering an immune response.
- Here, even CAR-T cells engineered to specifically target a patient’s unique tumour are unable to access it, suppressing their ability to kill tumour cells.

Synthetic Notch Receptor (SynNotch):

Researchers have developed a new synthetic receptor that could complement the first CAR design.
This receptor, called synthetic Notch receptor, or synNotch, is based on the natural form of Notch in the body, which plays an important role in organ development across many species.
Similar to CARs, the outside of synNotch has a binder that allows T cells to stick to tumour cells.
Unlike CARs, the inside of synNotch has a protein that is released when a T cell binds to the tumour.
This protein, or transcription factor, allows researchers to better control the T cell by inducing it to produce a specific protein.

Use of synNotch in cancer treatment:

One of the most useful applications of synNotch thus far has been to use it to ensure that engineered T cells are only activated when bound to a tumour cell and not healthy cells.
If successful, the T cells will now require both CAR and synNotch receptors to recognize tumours, this increases the precision of T cell killing.
Then it could be used to improve CAR-T cell therapy against solid tumours by inducing them to produce more of the inflammatory cytokines, such as IL-2, that enable them to kill tumour cells.
So researchers have designed CAR-T cells to produce IL-2 using synNotch.
Now, when a CAR-T cell encounters a tumour, it produces IL-2 within the tumour instead of outside it, avoiding causing harm to surround healthy cells.
Because synNotch is able to bypass the barriers tumours put up, it is able to help T cells amp up and maintain the amount of IL-2 they can make, allowing the T cells to keep functioning even in a hostile microenvironment.