Universal Tumor Killers
Immunotherapy is one of the new paradigms of cancer treatment, in which T–lymphocytes are taken from the patient's body, modified to search for and destroy cancer cells and returned to the blood. The most widely used CAR-T therapy is personalized for a specific patient and targeted at only a few types of cancer. It has not proven effective in solid tumors, which make up the vast majority of cancers.
Researchers from Cardiff University have discovered T-lymphocytes with a new type of T-cell receptors that recognize and kill cancer cells of many tumors, while ignoring healthy tissues.
This T-receptor recognizes a molecule on the surface of cancer cells, characteristic of a wide range of tumors, as well as many normal cells of the body. Surprisingly, the new T-receptor is able to distinguish between healthy and cancer cells, killing only the latter.
How does the new T-cell receptor work?
Normal T lymphocytes scan the surface of other cells to find abnormal proteins and eliminate cancer cells that express them, but ignore cells that contain only "normal" proteins.
The search engine recognizes small fragments of cellular proteins that are bound to molecules on the cell surface – the human leukocyte antigen (HLA), allowing T-killers to see what is happening inside cells by scanning their surface.
HLA varies greatly in different people, which prevented scientists from creating a single immunotherapy method that would target most cancers in all people.
A new study describes a unique T-cell receptor that can recognize many cancers through a single HLA-like molecule called MR1. Unlike HLA, MR1 is the same in all people – this makes it extremely attractive for immunotherapy.
What did the researchers show?
T cells equipped with the new receptor have been shown to kill lung, skin, blood, colon, breast, prostate, ovarian, kidney and cervical cancer cells, while ignoring healthy cells.
To test the therapeutic potential of these cells in vivo, the researchers injected MR1-recognizing T-killers into mouse models of human cancer with the human immune system.
The experiment showed promising results for cancer treatment, which, according to the researchers, were comparable to the currently approved CAR-T therapy in similar model animals.
The Cardiff team was also able to show that the T cells of melanoma patients modified to express this new T-receptor can destroy not only the cancer cells of the host patient, but also the cancer cells of other patients, regardless of the type of its HLA.
The new T-cell receptor has such a wide tropicity to cancer cells, which allows us to hope for the "universality" of this therapy. Modern methods of treatment can be used only in a minority of patients and against a smaller number of types of cancers.
What's next?
Experiments are currently underway to find out the exact molecular mechanism by which the new T-receptor distinguishes healthy cells from cancer cells.
The researchers believe that it may be due to changes in cellular metabolism, which are caused by various intermediary molecules presented on the surface of cancer cells using MR1.
The Cardiff-based group hopes to test the new approach on patients by the end of this year after successful safety trials.
Article by M.D.Crowther et al. Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1 is published in the journal Nature Immunology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru .