A wedge is knocked out with a wedge
Immunotherapy, which involves the body's own immune system in the fight against cancer, occupies an important place in oncology and gives many patients a chance to recover. Unfortunately, this treatment can be expensive, cause severe side effects and work only in some patients.
Researchers from the Pritzker School of Molecular Engineering (PME) at the University of Chicago have developed a new therapeutic vaccine that uses a patient's own cancer cells to train his immune system to detect and destroy cancer. In a study on mice, it stopped the growth of melanoma and protected it from relapses for a long time.
In many ways, the vaccine works like a traditional attenuated (weakened) vaccine: it uses a less powerful version of the pathogen (here, the patient's own cancer cells, which are irradiated before injection) to train the immune system to fight the disease.
However, this is not a preventive measure, but a therapeutic one, that is, the vaccine activates the immune system to destroy cancer cells anywhere in the body. To create it, Professor Melody Schwartz and her colleagues used mouse melanoma cells, and then modified them to secrete vascular endothelial growth factor C (VEGF-C).
VEGF-C causes the growth of lymphatic vessels, which is usually considered a sign of metastasis. But recently it has been shown that tumors that activate the surrounding lymphatic vessels become much more sensitive to immunotherapy and contribute to the "awakening" of T cells, leading to a more persistent and long-lasting immune response.
Immune System Training
The strategy of using the patient's own irradiated tumor cells in a therapeutic vaccine was previously developed by Glenn Dranoff and his colleagues from the Novartis Institute for Biomedical Research. They developed GVAX, a cancer vaccine that has been tested in clinical trials.
The authors decided to try this approach with VEGF-C rather than with the cytokine used in GVAX. They called this strategy VEGFC-vax.
After modifying the cells to express VEGF-C, the research team irradiated them so that they died within a few weeks. Intradermal administration of such dying cancer cells to mice led to the accumulation and activation of immune cells that were able to recognize and kill real cancer cells growing on the opposite side of the mouse body from the injection. Because each tumor has its own unique signature of hundreds of molecules that the immune system can recognize, vaccination has contributed to a broad and persistent immune response.
VEGFC-vax led to the arrest of tumor growth in all experimental mice. It also formed an immunological memory, preventing the appearance of new tumors after 10 months, when cancer cells were reintroduced.
This shows that therapy can provide long-term protection against metastases and relapses.
Potential therapy for many types of cancer
Unlike immunotherapeutic strategies that stimulate the immune system as a whole, such as checkpoint inhibitors or cytokines currently in preclinical development, the new immunotherapy with VEGF-C activates only tumor-specific immune cells. Theoretically, this would avoid the common side effects of immunostimulants, including immunotoxicity and even death.
Unlike highly specific methods, for example, CAR-T therapy, which work only against tumor cells that express pre-identified tumor markers, VEGFC-vax can train immune cells to recognize a large number and variety of tumor-specific antigens. More importantly, these antigens do not need to be identified in advance.
Researchers are working to test this strategy on models of breast cancer and colon cancer, and believe that theoretically it can work on any type of cancer. They hope to eventually bring this therapy to clinical trials.
Article by M.S.Sasso et al. Lymphangiogenesis-inducing vaccines elicit potent and long-lasting T cell immunity against melanomas published in the journal Science Advances.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Pritzker School of Molecular Engineering: Exploiting cancer cells to aid in their own destruction.