Immunotherapy, which employs the body ‘s own immune system to fight cancer, has given many cancer patients a new way to treat the disease.
But many cancer immunotherapy treatments can be expensive, have devastating side effects, and only work in a fraction of patients.
Researchers at the Pritzker School of Molecular Engineering at the University of Chicago have developed a new therapeutic vaccine that uses the patient’s own tumor cells to train their immune system to detect and kill cancer.
The vaccine, which is introduced into the skin just like a traditional vaccine, stopped the growth of melanoma tumors in mouse models. It worked even in the long run, destroying new tumors long after the treatment was given.
The results were published March 24 in the journal Advances in science.
“This is a new strategy for immunotherapy,” he said. Melody Swartz, who led the research. “It has the potential to be more effective, cheaper and much safer than many other immunotherapies. It is a truly personalized treatment that has the potential to overcome many issues that arise with other treatments.”
Hiring a broad immune response
In many ways, the vaccine works like a traditional flu vaccine: it uses a less potent version of the pathogen (here, the patient ‘s own cancer cells, which are lethal irradiated before being injected) to train the immune system to fight the disease.
However, rather than a protective measure, this is a therapeutic vaccine, meaning that it activates the immune system to destroy cancer cells anywhere in the body. To create it, Swartz and her team used melanoma cells from mice and then engineered them to grow vascular endothelial growth factor C (VEGF-C).
VEGF-C causes tumors to attach strongly to the body’s lymphatic system, which is usually considered bad for the patient, as it can promote metastasis. However, the team recently found that when tumors activate surrounding lymphatic vessels, they are much more sensitive to immunotherapy and stimulate “bystander” T cell activity, leading to a stronger and more immune response. permanent.
The team then had to figure out how they could reap the benefits of lymphatic activation in a therapeutic strategy while avoiding the potential risks from lymphatic. metastasis.
‘Training’ the immune system
Maria Stella Sasso, a postdoctoral companion and first author of the paper, tested many different strategies before setting them up for the vaccination method, which allowed for protective “training” in a site that was far from the true tumor.
The strategy for the use of the patient’s own irradiated tumor cells in therapeutic vaccination was previously established by Glenn Dranoff and colleagues at the Novartis Institutes for BioMedical Research. Dranoff and the team developed GVAX, a cancer vaccine that has been proven safe in clinical trials. Sasso decided to try this approach with VEGF-C instead of the cytokine used in GVAX. She named it “VEGFC-vax.”
After inventing the cells to express VEGF-C, the research team irradiated them, so they would die within a few weeks. When they returned the cells to the skin of mice, they found that the dying tumor cells could attract and activate the immune cells, which could then identify and kill the true tumor cells that were grow on the other side of the mouse. Because each tumor has its own unique signature of hundreds of molecules that the immune system can recognize, the vaccine stimulated a strong, robust immune response.
This inhibited the growth of tumors in all mice. It also led to immunological memory, inhibiting the growth of new tumors when tumor cells were reintroduced 10 months later.
“This demonstrates that the treatment could provide long-term efficacy against metastasis and recurrence,” said Swartz, William B. Ogden Professor of Molecular Engineering.
Possible therapy for many types of cancers
Sensibly, this is the first strategy to take advantage of the benefits of local lymphatic vessel activation for a stronger and more specific immune response against tumor cells.
Unlike immunotherapeutic strategies that stimulate the immune system in a general way, such as checkpoint inhibition or the many cytokines present in preclinical development, this new immunotherapy activates only specific immune cells tumors. Theoretically, this would avoid common side effects of immune stimulants, including immunotoxicity and even death.
And while many other cancer immunotherapies, such as CAR-T cell therapy, are tumor-specific, these strategies only work against tumor cells that elicit specific pre-identified tumor symptoms to the tumor. it is called antigens. Eventually cancer cells can get over these treatments by peeling off these symptoms or suppressing them, for example.
VEGFC-vax, however, can train immune cells to recognize large numbers and combinations of tumor-specific antigens. More importantly, these antigens do not need to be identified in advance.
The researchers are working to test this strategy on breast and colon cancers and believe it could theoretically work on any type of cancer. They hope to eventually take this treatment to clinical trials.
“We believe this holds great promise for the future of personalized cancer immunotherapy,” Swartz said.
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