Discovery may treat all types of cancers

One-size-fits-all cancer therapy.

Cardiff scientists have discovered a new type of killer T-cells to treat all cancers.

They have equipped with a new type of T-cell receptor (TCR), which recognizes and kills most human cancer types while ignoring healthy cells. It identifies a molecule present on the surface of a wide range of cancer cells as well as in many of the body’s healthy cells. Most importantly, it can categorize cancer cells d healthy cells.

How does this new TCR work?

TCR can recognize many types of cancer via a single human leukocyte antigen (HLA) like a molecule called MR1. Unlike HLA, MR1 does not vary in the human population – meaning it is a hugely attractive new target for immunotherapies.

When tested in the lab, scientists found that their new method can kill lung, skin, blood, colon, breast, bone, prostate, ovarian, kidney, and cervical cancer cells while ignoring healthy cells.

To test the remedial capability of these els in vivo, scientists infused T-cells ready to perceive MR1 into mice bearing human cancer growth and with a social immune system.

This demonstrated empowering cancer-clearing results, which the specialists said was practically identical to the now NHS-approved CAR-T therapy in a comparable animal model.

Scientists further able to show that T-cells of melanoma patients modified to express this new TCR could destroy not only the patient’s cancer cells but also other patients’ cancer cells in the laboratory, regardless of the patient’s HLA type.

Professor Andrew Sewell, the lead author of the study and an expert in T-cells from Cardiff University’s School of Medicine, said, “it was “highly unusual” to find a TCR with such broad cancer specificity, and this raised the prospect of “universal” cancer therapy.”

“We hope this new TCR may provide us with a different route to target and destroy a wide range of cancers in all individuals.”

“Current TCR-based therapies can only be used in a minority of patients with a minority of cancers. Cancer-targeting via MR1-restricted T-cells is an exciting new frontier – it raises the prospect of ‘one-size-fits-all’ cancer treatment, a single type of T-cell that could be capable of destroying many different types of cancers across the population.”

Scientists are still testing their method to determine the precise molecular mechanism by which the new TCR distinguishes between healthy cells and cancer. It may work by sensing changes in cellular metabolism, which causes different metabolic intermediates to be presented at the cancer cell surface by MR1.

Professor Oliver Ottmann, Cardiff University’s Head of Haematology, whose department delivers CAR-T therapy, said: “This new type of T-cell therapy has enormous potential to overcome current limitations of CAR-T, which has been struggling to identify suitable and safe targets for more than a few cancer types.”

Professor Awen Gallimore, of the University’s division of infection and immunity and cancer immunology lead for the Wales Cancer Research Centre, said: “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 personalized T-cells.

“This is truly exciting and potentially a great step forward for the accessibility of cancer immunotherapy.”

The research was funded by the Wellcome Trust, Health and Care Research Wales, and Tenovus.

The study is published in the journal Nature Immunology.

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