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Cardiff University researchers have discovered a new a new type of T cell that can kill a variety of cancers, with the hope of creating a general "one-size-fits-all" T cell therapy.
CAR T cell therapy today is commonly "customized" for each cancer patient using their own T cells. A patient has their immune system cells removed, they are then engineered to hit a target of cancer cells (like BCMA in myeloma) and then the T cells are returned to the patient. They have been most commonly used in blood cancers like multiple myeloma, leukemia and lymphoma and have not been particularly effective in solid tumors.
The UK researchers used a gene editing screening technology called CRISPR to find a new type of T cell receptor that finds and kills most human cancer types (including solid tumors), while ignoring healthy cells. The T cell targets the MR1 protein which is independent of the human leukocyte antigen (HLA) typing.
You may be familiar with HLA typing that is done for allogenic stem cell transplant. When myeloma patients receive such a donor transplant, their HLA typing must be close to the donor's.
Differences in HLA typing is one reason that a single CAR T therapy has not yet been developed for all cancer patients. However, this HLA-like molecule called MR1 can be recognized by the new T cell receptor. MR1 is consistent in the human population and will be an incredibly attractive new target for immunotherapies.
These findings offer opportunities for HLA-independent, pan-cancer, pan-population immunotherapies.
The MR1 protein is important in developing a certain type of cells called Mucosal-associated invariant T (MAIT) cells. These MAIT cells have shown to have a role in multiple myeloma. MAIT cells are the most abundant population of antimicrobial T cells in humans. They are involved in a large number of infectious and non-infectious diseases and are related to the inflammatory cytokine IL-17A.
The researchers injected T cells that could recognized MR1 in mice who also were given a human cancer and a human immune system and it showed similar cancer killing impact as current CAR T therapies. They also modified the T cells of melanoma (skin cancer) patients and found that the new TCR could kill not only the individual melanoma patient's cancer cells, but also the cancer cells of other patients in the lab, independent of the patient's HLA type. They also found that even low levels of MR1 expression were linked to the death of the cancer cells and not the healthy cells.
Further multi-year testing is necessary to bring this discovery to a Phase I clinical trial in humans. The group is optimistic that targeting this new T cell receptor and MR1 protein may "further open up opportunities for therapeutic vaccination for many cancers in all individuals."
This would be a truly amazing discovery in immunotherapy for multiple myeloma and many other cancers.
Cardiff University researchers have discovered a new a new type of T cell that can kill a variety of cancers, with the hope of creating a general "one-size-fits-all" T cell therapy.
CAR T cell therapy today is commonly "customized" for each cancer patient using their own T cells. A patient has their immune system cells removed, they are then engineered to hit a target of cancer cells (like BCMA in myeloma) and then the T cells are returned to the patient. They have been most commonly used in blood cancers like multiple myeloma, leukemia and lymphoma and have not been particularly effective in solid tumors.
The UK researchers used a gene editing screening technology called CRISPR to find a new type of T cell receptor that finds and kills most human cancer types (including solid tumors), while ignoring healthy cells. The T cell targets the MR1 protein which is independent of the human leukocyte antigen (HLA) typing.
You may be familiar with HLA typing that is done for allogenic stem cell transplant. When myeloma patients receive such a donor transplant, their HLA typing must be close to the donor's.
Differences in HLA typing is one reason that a single CAR T therapy has not yet been developed for all cancer patients. However, this HLA-like molecule called MR1 can be recognized by the new T cell receptor. MR1 is consistent in the human population and will be an incredibly attractive new target for immunotherapies.
These findings offer opportunities for HLA-independent, pan-cancer, pan-population immunotherapies.
The MR1 protein is important in developing a certain type of cells called Mucosal-associated invariant T (MAIT) cells. These MAIT cells have shown to have a role in multiple myeloma. MAIT cells are the most abundant population of antimicrobial T cells in humans. They are involved in a large number of infectious and non-infectious diseases and are related to the inflammatory cytokine IL-17A.
The researchers injected T cells that could recognized MR1 in mice who also were given a human cancer and a human immune system and it showed similar cancer killing impact as current CAR T therapies. They also modified the T cells of melanoma (skin cancer) patients and found that the new TCR could kill not only the individual melanoma patient's cancer cells, but also the cancer cells of other patients in the lab, independent of the patient's HLA type. They also found that even low levels of MR1 expression were linked to the death of the cancer cells and not the healthy cells.
Further multi-year testing is necessary to bring this discovery to a Phase I clinical trial in humans. The group is optimistic that targeting this new T cell receptor and MR1 protein may "further open up opportunities for therapeutic vaccination for many cancers in all individuals."
This would be a truly amazing discovery in immunotherapy for multiple myeloma and many other cancers.
about the author
Jennifer Ahlstrom
Myeloma survivor, patient advocate, wife, mom of 6. Believer that patients can contribute to cures by joining HealthTree Cure Hub and joining clinical research. Founder and CEO of HealthTree Foundation.
