British scientists recently announced the discovery of a new type of cancer-killing T-cell. Having partnered with a biotechnology company, the group have developed T-cell receptor (TCR)-based immunotherapies. They hope the result will be a “one-size-fits-all” cancer therapy!
This group from Cardiff University has identified a T-cell modulation, a new type of killer T-cell. This T-cell clone recognizes and kills different types of human cancer. It also ignores healthy, non-cancerous cells. This discovery has triggered hope that a universal cancer therapy is possible. Researchers reported in Nature Immunology that these T-cells killed lung, skin, blood, colon, breast, bone, prostate, ovarian, kidney and cervical cancer.
The Cardiff researchers have now entered a partnership with Ervaxx will eventually bring their discovery to patients.
T-cell therapies for cancer are the latest paradigm in cancer treatments. There are current therapies available where immune cells are removed from the patient, genetically-modified, and then returned to a patient’s blood. These modified T-cells seek out and destroy cancer cells in the blood. They are not successful in solid tumors.
In contrast, however, the newly discovered T-cell attaches to a molecule on cancer cells called MR1, which does not vary in humans. It is hoped that this approach might eventually be applied as an almost instant ‘off-the-shelf’ treatment.”
Professor Andrew Sewell, the lead author of the study at Cardiff University, cautions people from becoming overly optimistic too soon about Cardiff’s findings. He said, “while the scientists’ discovery is potentially game-changing, an actual universal cancer therapy could be years away. I would really like to stress that we have not cured a patient—our results were all laboratory-based, albeit with patient T-cells and cancer cells. Curing cancer in a culture dish and curing it in a patient are two very different things.”
When Cardiff researchers injected the new immune cells into mice with a human immune system and into a human blood cancer line, the cancer cells were cleared to a level seen with CAR-T cells in the same mouse model, Sewell said. The group further demonstrated that equipping T-cells of skin cancer patients with the new receptor-induced them to destroy not only the patient’s own cancer cells but also other patients’ cancer cells in the laboratory, he said.
“Cardiff researchers have now discovered T-cells equipped with a new type of T-cell receptor (TCR) which recognizes and kills most human cancer types, while ignoring healthy cells. This TCR recognizes a molecule present on the surface of a wide range of cancer cells as well as in many of the body’s normal cells but, remarkably, is able to distinguish between healthy cells and cancerous ones, killing only the latter.”
Sewell further stated his interest is in killer T-cell. “Killer T-cells are fascinating as they have the unique ability to see inside other body cells and scan them for anomalies.” he said. “Conventionally, killer T-cells scan the molecular machines inside cells called proteins. A clever system presents bits of all the proteins inside each cell on its surface bound to molecular platforms called HLA [Human Leukocyte Antigen]. Normal, healthy body cells only present bits of normal proteins, and these are ignored by killer T-cells. If a cell is, for instance, infected with a virus, then it will contain some proteins of viral origin and bits of these will be displayed on the surface of the infected cell. Killer T-cells can recognize these protein fragments as ‘foreign’. This activates the killer T-cell to destroy the infected body cell and all its contents, including the virus. In this sense, killer T-cells act as a sophisticated ‘seek and destroy’ weapon.”
“Now that we know that these types of cells exist, we can actively look for others that work by a similar mechanism. Indeed, we have already found similar broadly tumoricidal, ‘HLA-agnostic’ killer T-cells that see cancers via different surface molecules. The molecules targeted by these cells were also discovered using the CRISPR library approach. CRISPR gene editing has been a real game-changer.”
Sewell said the next step will begin with safety testing on further healthy human cell lines in the laboratory. History has shown, he said, that some T-cells could attack things we don’t want them to. “We have already demonstrated that our new T-cell does not respond to 20 healthy cell types,” he said. “The human body has many more cell types than this so, as best we can, we need to rule out that this T-cell does not attack any further healthy human cell types. The new MR1-binding receptor has a natural sequence isolated from a healthy donor and thus the likelihood that it will attack healthy tissue is unlikely.”
In any event, Sewell said “it is important for people to acknowledge that this discovery has not been tested outside of the laboratory and not yet in human beings. It is impossible to reconstitute a whole human body as individual cell types in the laboratory, so after passing an accepted level of safety testing in this way, the next step is a first-in-man trial” Sewell said. “In order to minimize the risk, it is likely that the first time this type of T-cell is used in man, the T-cells will ‘transiently’ [impermanently] express the relevant T-cell receptor and be given in low numbers, with escalation from there once safety is demonstrated. This way if there is any autoimmune attack it will be at a low level and short-lived, so hopefully do minimal damage.”
While Sewell hesitated at giving a timeline for when an actual universal cancer therapy or cure could be expected, he is hopeful that clinical trials may start in the next few years once further laboratory safety testing is completed.