Recently Discovered Killer T-Cell Raises Hopes of Universal T-Cell Cancer Therapy

Recently Discovered Killer T-Cell Raises Hopes of Universal T-Cell Cancer Therapy

Researchers at Cardiff University have discovered a new killer T-cell that attacks and kills most cancer cells, raising hopes it could be used as a universal cancer treatment.

The researchers were analyzing blood from a Welsh blood bank looking for immune cells that kill bacteria when they discovered the new type of T-cell. The new T-cell was equipped with a previously unseen T-cell receptor that recognized a molecule present on the surface of most cancerous cells in humans, which could allow it to be used as a one-size-fits-all cancer therapy. In their lab studies, the researchers demonstrated the new T-cell killed blood, breast, bone, prostate, ovarian, kidney, cervical, skin and lung cancer cells.

The T-cell is believed to be very rare, although the receptor could be more common but inactivated in most individuals. At this stage, relatively little is known about this new killer T-cell.

T-cells search for abnormal proteins on the surface of cells. When an abnormal protein is discovered, the cells are attacked. If normal proteins are found on the cell surface, the cells are ignored. T-cells have been harnessed and used as a treatment for certain types of cancer, but their uses are limited. They only attack specific types of cancer and the treatments are personalized for each patient, which makes treatment expensive.

Credit: Professor Andrew Sewell, Cardiff University

T-cell therapy involves harvesting T-cells from a patient, altering them in the lab to recognize molecules on the surface of cancer cells, growing them and then reintroducing them into a patient in large numbers. CAR-T therapy has been shown to be effective at treating blood cancers but does not work on solid tumors. Most human cancers form solid tumors. Another form of T-cell therapy, TCR-T therapy, has been shown to attack some types of cancer with solid tumors. However, these therapies work by locking onto cell-surface molecules called human leukocyte antigen (HLA). Since HLA varies from individual to individual, a universal cancer treatment has not yet been developed. Treatment is personalized for each patient.

The new T-cell recognizes an HLA-like molecule called MR1, which does not vary from individual to individual. MR1 is present on the surface of most cancer cells, and since it does not vary from individual to individual, banks of the new T-cell could be created and could serve as an off-the-shelf treatment for patients.

The researchers tested the new immune cells in mice with human cancer and a human immune system with positive results. They also showed in the lab that T-cells of skin cancer patients that were modified to express the new receptor were also effective at killing cancer cells from other patients.

“Current TCR-based therapies can only be used in a minority of patients with a minority of cancers,” said Professor Andrew Sewell, lead author of the study. “We hope this new TCR may provide us with a different route to target and destroy a wide range of cancers in all individuals.”

The researchers are now investigating how the T-cells differentiate between cancer cells and healthy cells. Before human trials, the researchers will need to confirm that the T-cells only attack cancer cells and not healthy cells. All being well, the researchers hope to trial the new T-cell therapy in human patients by November 2020 and if all goes to plan, the new treatment could be used in patients in a few years.

“If this transformative new finding holds up, it will lay the foundation for a ‘universal’ T-cell medicine, mitigating against the tremendous costs associated with the identification, generation and manufacture of personalised T-cells,” said Professor Awen Gallimore, of Cardiff University’s division of infection and immunity and cancer immunology lead for the Wales Cancer Research Centre.

You can read more about the study in the paper – Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1- which was recently published in the journal Nature Immunology. DOI: 10.1038/s41590-019-0578-8

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