Gel against cancer recurrence
Surgical removal of solid tumors often does not lead to a complete recovery of patients due to single cancer cells that remain in the tissues after surgery and give growth to new tumors.
A team of researchers from the University of Wisconsin-Madison, the University of California at Los Angeles, the University of North Carolina and Zhejiang University has developed and successfully tested on mice a new biodegradable gel containing a cocktail of immunostimulating cytokines, platelets with antibodies and modified CAR-T cells. The composition is injected into the resection cavity after surgical removal of the tumor and fights the remaining cancer cells. Three weeks after the removal of the tumor in mice that were injected with gel during surgery, the tumors of mice receiving specialized gel were about 60 times smaller than in animals that did not receive treatment.
Micrography of antitumor gel. The biodegradable gel (blue color) contains platelets loaded with antibodies (red color) and modified T cells (yellow color).
The method is based on the principle of immunotherapy, when the patient's own T-lymphocytes are reprogrammed so that they attack and destroy cancer cells. Currently, CAR-T therapy is approved for the treatment of blood oncological diseases (lymphoma, leukemia), but it is not effective against solid tumors, such as melanoma or breast cancer, because modified cells are more difficult to concentrate in them. And although such tumors can be surgically removed, cancer cells often remain in the body and can cause cancer to grow again. To avoid relapse after surgery, the patient undergoes chemotherapy or radiation therapy, which cause serious side effects, but do not always prevent relapse.
This motivated scientists to find another way to combat relapses. They focused on modifying CAR-T therapy to make it effective against solid tumors. To do this, it was necessary to make a number of changes. First, the researchers placed the cytokine interleukin-15 (IL-15), which is necessary for the proliferation of T-killers, in a biodegradable hyaluronic acid hydrogel. Secondly, they added platelets, preloading them with antitumor antibodies. The fact is that the ineffectiveness of CAR-T-cell therapy against solid tumors is associated with the so-called switch that cancer cells use to inactivate T-lymphocytes. These antibodies block the switch, reactivating the T cells. And finally, at the third stage, the researchers injected reprogrammed T cells into the gel.
The biocompatible and biodegradable gel provides a slow release of the active components after application to the niche formed after the removal of the tumor.
The antitumor cocktail gel was tested on mouse models of human melanoma. The researchers surgically removed most of the tumor, and then either gel or saline was injected into the resected cavity. After three weeks, tumors in mice from the saline group increased significantly, while in mice treated with gel, they practically did not grow.
In another experiment, each mouse had two melanomas, one on each side of the body. The researchers removed only one and injected a gel in its place. The modified T cells moved to another tumor, slowing its growth. This means that the strategy of local treatment can also have a systemic effect.
Despite the promising results, several more studies are to be conducted to understand how the body's own platelets affect modified platelets, how well the gel works with other types of cancer and to test it on large animals.
Article Q.Hu et al. Inhibition of post-surgery tumour recurrence via a hydrogel releasing CAR-T cells and anti-PDL1-conjugated platelets is published in the journal Nature Biomedical Engineering.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to the University of Wisconsin–Madison: Gel loaded with cancer-fighting cells keeps tumors in check after surgery in mice.