Researchers at Cardiff University have discovered a new type of killer T-cell that offers hope of a “one-size-

Researchers at Cardiff University have discovered a new type of killer T-cell that offers hope of a one-size-fits-all cancer therapy.
T-cells 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. 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 was comparable to the now NHS-approved CAR-T therapy in a similar animal model.
The Cardiff group were further able to show that T-cells of melanoma patients modified to express this new TCR could destroy not only the patients own cancer cells, but also other patients cancer cells in the laboratory, regardless of the patients HLA type.
CAR-T and T-Cells
T-cell therapies for cancer – where immune cells are removed, modified and returned to the patients blood to seek and destroy cancer cells – are the current hottest thing in cancer treatments. The most widely-used therapy, known as CAR-T, is personalized to each patient but targets only a few types of cancers and has not been successful for solid tumors, which make up the vast majority of cancers.
T-cell therapies have been making slow progress because each type of cancer needs specific modifications that require their own clinical trials.
Cardiff researchers have now discovered T-cells equipped with a new type of T-cell receptor (TCR) which recognises and kills most human cancer types, while ignoring healthy cells.
Nature Immunology – Genome-wide CRISPRCas9 screening reveals ubiquitous Tcell cancer targeting via the monomorphic MHC class I-related protein MR1.
How does this new TCR work?
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 recognizes small parts of cellular proteins that are bound to cell-surface molecules called human leukocyte antigen (HLA), allowing killer T-cells to see whats 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.
Abstract
Human leukocyte antigen (HLA)-independent, T cellmediated targeting of cancer cells would allow immune destruction of malignancies in all individuals. Here, we use genome-wide CRISPRCas9 screening to establish that a T cell receptor (TCR) recognized and killed most human cancer types via the monomorphic MHC class I-related protein, MR1, while remaining inert to noncancerous cells. Unlike mucosal-associated invariant T cells, recognition of target cells by the TCR was independent of bacterial loading. Furthermore, concentration-dependent addition of vitamin B-related metabolite ligands of MR1 reduced TCR recognition of cancer cells, suggesting that recognition occurred via sensing of the cancer metabolome. An MR1-restricted T cell clone mediated in vivo regression of leukemia and conferred enhanced survival of NSG mice. TCR transfer to T cells of patients enabled killing of autologous and nonautologous melanoma. These findings offer opportunities for HLA-independent, pan-cancer, pan-population immunotherapies.
SOURCES- University of Cardiff, Nature ImmunologyWritten By Brian Wang, Nextbigfuture.com
Brian Wang is a prolific business-oriented writer of emerging and disruptive technologies. He is known for insightful articles that combine business and technical analysis that catches the attention of the general public and is also useful for those in the industries. He is the sole author and writer of nextbigfuture.com, the top online science blog. He is also involved in angel investing and raising funds for breakthrough technology startup companies.
He gave the recent keynote presentation at Monte Jade event with a talk entitled the Future for You.  He gave an annual update on molecular nanotechnology at Singularity University on nanotechnology, gave a TEDX talk on energy, and advises USC ASTE 527 (advanced space projects program). He has been interviewed for radio, professional organizations. podcasts and corporate events. He was recently interviewed by the radio program Steel on Steel on satellites and high altitude balloons that will track all movement in many parts of the USA.
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