Prevention of cancer recurrence
Researchers from the Dana-Farber Cancer Research Institute in Boston (Dana-Farber Cancer Institute, USA) have proposed a new cancer treatment strategy aimed at preventing relapses and metastases, consisting in injecting the gel directly into the surgical wound immediately after resection of the tumor.
Surgical removal of the primary tumor is the main method of treatment of most solid tumors. However, it does not exclude the risk of repeated tumor growth or the appearance of distant metastases. The fact is that after excision of the neoplasm, a small group of cancer cells may remain, which makes a complete cure impossible.
In addition, the development of the tumor is accompanied by the migration of immune cells that form the so-called microenvironment. One group of cells suppresses local immunity in order to reduce the spread of tumor waste products and "protect" the body from intoxication. Another group of cells, on the contrary, is actively trying to fight cancer cells and form antitumor immunity. During the resection of the neoplasm, T-killers are removed, which could destroy the remaining cancer cells after the operation.
And finally, surgical excision of the tumor leads to a decrease in the body's resistance associated with the presence of a postoperative wound and its healing. Such temporary immunosuppression is a favorable condition for the spread of cancer cells throughout the body and the formation of metastases.
Immunotherapy could get rid of metastases and relapses, but systemic administration of drugs does not allow achieving sufficient concentration directly at the location of the primary tumor. This prompted the researchers to introduce the drug upon completion of surgical treatment immediately into the bed formed after excision of the tumor, and to form a new microenvironment that would stimulate the body's own forces to fight the remaining cancer cells.
An experiment was conducted on mice with a breast cancer model. The researchers removed the tumor, and a biodegradable gel with an immunostimulating drug was placed in the resulting bed. Slowly released, it activated local immunity and prevented the recurrence and metastasis of cancer.
The injected drug was a hydrogel disk with a diameter of about one and a half centimeters, consisting of biodegradable carbohydrates. Agonists of toll-like receptors (TLR7 and TRL8) and an interferon gene stimulator (stimulator of interferon genes, STING) were placed in it. The gradual destruction of the hydrogel was accompanied by the portioned release of active substances, which, in turn, led to an increase in the number of dendritic cells, T-killers and other lymphocytes, increased the production of interferon I.
As a result, the immunosuppressive microenvironment, which naturally forms after tumor resection, was replaced by an immunostimulating one.
The animals were monitored for several months. Survival in the experimental group was higher than among mice who received the same drug, but with a different delivery method. Both the percentage of recurrence of the primary tumor and the number of distant metastases in the lungs decreased.
Local immunotherapy was accompanied not only by effective treatment, but also by a low level of side effects. Thus, the mice from the experimental group did not lose weight, no biochemical markers of liver and kidney damage were found in the blood, the quantity and quality of the shaped elements corresponded to the norm.
Even after three months of follow-up, no relapses were detected. Repeated introduction of cancer cells into a healthy mammary gland did not lead to the development of a tumor. This, apparently, was due to the formation of a stable immunity to cancer cells.
The results were duplicated in experiments on mice with lung cancer and melanoma.
The authors conclude that their proposed treatment regimen combining surgical excision of the tumor with subsequent injection of a hydrogel with immunostimulants into the surgical wound could be effectively used to treat all types of solid tumors anatomically available for surgical treatment. Currently, they are busy adapting the method for testing in clinical trials involving sick people.
Article by C. G. Park et al. The extended release of perioperative immunotherapy prevents tumor recurrence and eliminates metastases is published in the journal Science Translational Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Dana-Farber Cancer Institute: Gradual release of immunotherapy at site of tumor surgery prevents tumors from returning and eliminates cancer spread in mouse study.