NEW ‘ATTACK CELL’ HOPE FOR CANCER
ANEW “killer cell” has been discovered by scientists which has the ability to attack all types of cancer.
Researchers at Cardiff University claim this breakthrough could lead to a “one-size-fits-all” cancer therapy being created, as opposed to current treatments which are personalised to each patient.
The new type of T-cell receptor, known as TCR for short, recognises and kills most human cancer types while ignoring healthy cells.
Previously, such therapy targeted only a few types of cancer and was not successful for solid tumours which make up the vast majority of cancers.
But now it is claimed the new TCR has the remarkable ability to distinguish between healthy cells and cancerous ones, killing only the latter.
The university’s researchers claim this breakthrough offers “exciting opportunities for pan-cancer, pan-population” treatments not previously thought possible.
Professor Andrew Sewell, lead author on the study and an expert in T-cells from Cardiff University’s School of Medicine, said: “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. It raises the prospect of a ‘one-size-fits-all’ cancertreatment – a single type of T-cell that could be capable of destroying many different types of cancers across the population.
“Previously, nobody believed this could be possible.”
T-cell therapies for cancer are the latest paradigm in cancer treatments.
They involve immune cells being removed, modified and returned to the patient’s blood to seek and destroy cancer cells.
The most widely-used therapy, known as CAR-T, is personalised to each patient, but targets only a few types of cancer and has not been successful for solid tumours.
Conventional T-cells scan the surface of other cells to find anomalies and eliminate cancerous cells – which express abnormal proteins – but ignore cells that contain only “normal” proteins.
The scanning system recognises small parts of cellular proteins that are bound to cell-surface molecules called human leukocyte antigen (HLA), allowing killer T-cells to see what’s occurring inside cells by scanning their surface.
HLA varies widely between individuals, which has previously prevented scientists from creating a single T-cell-based treatment that targets most cancers in all people.
But the Cardiff study, published today in Nature Immunology, describes a unique TCR that can recognise many types of cancer via a single HLA-like molecule called MR1. Unlike HLA, MR1 is does not vary in the human population, meaning it is a hugely attractive new target for immunotherapies.
T-cells equipped with the new TCR were shown, in the lab, to kill lung, skin, blood, colon, breast, bone, prostate, ovarian, kidney and cervical cancer cells while ignoring healthy cells.
To test the therapeutic potential of these cells in vivo (inside a living organism), the researchers injected T-cells able to recognise MR1 into mice bearing human cancer and with a human immune system.
This showed “encouraging” cancer-clearing results which the researchers said were comparable to the now NHS-approved CAR-T therapy in a similar animal model.
The Cardiff group was further able to show that T-cells of melanoma patients modified to express this new TCR could destroy not only the patient’s own cancer cells, but also other patients’ cancer cells in the laboratory, regardless of the patient’s HLA type.
Prof Sewell said it was “highly unusual” to find a TCR with such broad cancer specificity and this raised the prospect of “universal” cancer therapy.
Experiments are now under way to determine the precise molecular mechanism by which the new TCR distinguishes between healthy cells and cancer.
The researchers believe it may work by sensing changes in cellular metabolism which cause different metabolic intermediates to be presented at the cancer cell surface by MR1.
The Cardiff group hopes to trial this new approach in patients towards the end of this year following further safety testing.
Prof Sewell said a vital aspect of this ongoing safety testing was to further ensure killer T-cells modified with the new TCR recognise cancer cells only.
“There are plenty of hurdles to overcome. However, if this testing is successful, then I would hope this new treatment could be in use in patients in a few years’ time,” he said.
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 personalised T-cells.
“This is truly exciting and potentially a great step forward for the accessibility of cancer immunotherapy.”