Medical news today The immunotherapy revolution is inspiring a new and optimistic spirit in cancer medicine, but there are still many bumps in the road because this therapeutic approach is based on activating patients’ immune systems against the cancerous growth. It can only succeed if the immune system “sees” the tumor and recognizes it as foreign. While there are ways to hone this “visual acuity” of the immune system, these solutions are inherently limited, as by their very definition they must be customized for each and every patient.
But now he has developed a multidisciplinary and international team, led by Prof. Jordana Samuels and Dr. Avia Perry of the Weizmann Institute, a method that may allow more patients to enjoy personalized immunotherapy. The findings of the study on this subject were reported over the weekend (Friday) in the Journal of Scientific Investigation . Hebrew in Jerusalem, Prof. Stephen Rosenberg of the National Cancer Institute of the United States, Prof. Cyril Cohen of Bar Ilan University, Dr. Ansoman Satpati of Stanford University and other researchers.
The team identified using this method “a hot spot “Characteristic of a particularly violent subtype of melanoma skin cancer. The so-called ‘hot spots’ in malignancies are actually molecular structures. Which are displayed on top of the cancer cell membranes of many patients. These are a weak point that may expose the tumor to the immune system. These structures contain mutated protein fragments called neo-antigens. They can be detected by T cells of the immune system.
Once the targets are identified, T cells bind to neo-antigens and kill the cancer cells. This action of T cells is actually the ultimate goal of all types of immunotherapy. The problem so far has been that most neo-antigens are “boutique” proteins – stemming from unique mutations that characterize specific tumors, so when used for therapeutic purposes to stimulate the action of a particular patient’s T cells, the treatment is not suitable for other patients.
Only a pinch of neo-antigens formed as a result of common mutations, which characterize many patients, can be considered as “hot spots”, but extremely difficult to detect. The difficulty stems in part from the fact that they are displayed on cell membranes using protein arrays called HLAs, which in themselves appear in thousands of different versions, so if one also takes into account the multiple cancer mutations, millions of possible molecular patterns are obtained. Due to the huge variety, most of the hotspots have actually been discovered so far at random. In the new study, the team from the Department of Molecular Biology of the cell developed an approach to the systematic identification of hotspots.
Scientists first used algorithms to search international databases containing the genetic information of thousands of cancer patients. They focused on melanoma, the type of cancer being studied in Prof. Samuel’s lab, and looked for common mutations in oncogenes – carcinogenic genes – that are represented by common versions of HLA arrays. This is how some neo-antigens that were candidates for hotspots were identified and isolated in the laboratory to test how, if at all, T cells respond to them.
Using this new approach, the scientists identified a hotspot originating in RAS – Oncogen involved in about a third of all cancers of all types. The hot spot discovered is related to a version of RAS that causes a particularly violent type of melanoma in about 20% of patients. On top of the melanoma cells.The researchers then created engineered T cells that express the receptor and placed them in laboratory vessels with tissue samples from appropriate melanoma patients.After exposure to the hot spot, T cells underwent activation and destroyed the tumor cells in a targeted manner, i.e. only the cells carrying the hot spot.
Dr. Perry: “We exposed a neo-antigen that appears in thousands of melanoma patients each year and showed that it can be used to mark the tumor cells as a target for the destruction of the immune system. There is another important advantage to the new method: because the approach Based on hot spots derived from oncogenes expressed in each and every cell of the tumor, the treatment is likely to eliminate all the tumor cells, not just some of the tumor cells as may be the case with treatments targeting more boutique neo-antigens. “
Prof ‘Samuels:’ Our new approach may lead to ‘mass immunotherapy’, ie the development of T-cell receptors that detect hot spots and may be used to treat the group Extensive patients. Such treatments are expected to be cheaper and simpler to implement than preparing custom T cells. It is also possible to apply this approach to many different types of cancer, not just melanoma, and it is ripe to move into the development phase towards its use in hospitals. “
In order to promote the transition from the laboratory to the clinic,” Knowledge “, The intellectual property commercialization arm of the institute’s scientists, works to commercialize the technology through a company that is in the construction stages.