Accurate personalized medicine has taken the lead in oncological research and scientists are striving to improve in each patient, individually, the mechanism and the route to aim, in the most accurate way, at the appropriate therapeutic target. The directed therapies begin to multiply and in the Vall d'Hebron Institute of Oncology (VHIO), for example, they have reached one of their maximum exponents. Or the most literal, at least. It is an immunotherapy that, in fact, directs the immune system towards the tumor cells in a subgroup of breast cancer.
This research goes back more than 10 years ago, when the VHIO scientists found a protein present in a subtype of breast tumors, the HER2 +. It is the p95HER2 protein, a component found on the surface of tumor cells, but not in any healthy cell type. "We thought that this component could be used to direct the immune system towards tumor cells," recalls Dr. Joaquim Arribas, director of the VHIO Preclinical Research Program. And so it has been.
Scientists have designed an immunotherapy that It consists in the injection of an antibody that functions as a kind of magnet: they are called bispecific antibodies of T lymphocytes and, as its structure has two arms, it has the ability to target and stick to a certain protein and, at the same time, the other arm, join the cells of the immune system. In this case, the antibody used uses one of its binding sites to bind to the protein p95HER2 and with the other it attracts the T lymphocytes of the immune system to those tumor cells where the protein is deposited. Literally, the antibody guides the immune system to those malignant cells to destroy them without damaging any healthy tissue. "It's a way to create a physical bridge between the immune system and the tumor cells," says Arribas.
Researchers have successfully tested this treatment in animal models, but Arribas notes that "they are not remote models of patients with tumors." In fact, to develop the experiment, the scientists took samples of tumors from real patients and their blood to reproduce, in the laboratory, the immune system of these patients. The VHIO team has published this finding in the journal Science Translational Medicine.
Although they have only tried it, for now, in preclinical studies, the good results predict a clinical trial with patients in one or two years, admits Arribas. This treatment is designed for patients with a breast tumor of the HER2 + subgroup that express the p95HER2 protein and have not responded to other therapies. HER2 + breast cancer has effective treatments in 70% of cases, but the other 30% of patients are left without therapeutic alternatives.
Immunotherapy has shown positive effects in patients with metastases when all other available therapies fail. However, the stimulation of the defensive army of the human body itself can also have unexpected side effects, such as the immune system attacking healthy cells and causing autoimmune diseases. This new therapy, however, insofar as it redirects the immune system only to malignant cells, can expand the therapeutic arsenal, also in other types of cancer. In fact, Arribas admits that "there is evidence that it can work in 15% of stomach tumors." The researchers add that, since this mechanism is directed to the home of the tumor cells, without damaging the healthy tissue, it could also be used for chemotherapies that already exist and that are not used because of their high toxicity.