Hydrogel for immunotherapy
Developed by Rice University researchers in collaboration with colleagues from the University of Texas, a hydrogel, a slow-releasing immunotherapy drug, provides effective destruction of malignant cells.
The images show the reaction of malignant cells to the gradual release of the immunotherapy drug for 3 days. The dose of the drug increases from top to bottom, while living cells (green) are replaced with dead cells (red) as the dose increases. The scale division corresponds to 50 micrometers.
The image obtained with the help of a scanning electron microscope demonstrates self-assembling nanofibers forming a hydrogel.
Clinical studies of immunotherapeutic drugs have demonstrated their powerful antitumor effect. However, a serious disadvantage of this approach is the rapid elimination of drugs from the body, which causes the need for its repeated injections.
A potential solution to this problem is the use of a drug developed by the authors, called STINGel. It is a combination of a new class of immunotherapeutic drug – a STING agonist (interferon gene stimulator) – and an injectable hydrogel that gradually releases the drug, creating its stable concentration necessary to activate the immune system against cancer cells.
The head of the study, Professor Jeffrey Hartgerink, is a pioneer in the development of self-assembling hydrogels based on multi-domain peptides. These hydrogels mimic the extracellular matrix, promoting cell growth and vascular network to repair tissue damage. Initially having a liquid consistency, the hydrogel under the conditions of the body acquires a semi-liquid consistency and slowly degrades over time. Saturation of the initially cell-friendly hydrogel with the above-mentioned immunotherapeutic drug belonging to the class of cyclic dinucleotides made it fatal for tumors.
The effectiveness of STINGel was evaluated both in experiments on cell cultures and on an animal model. In the second case, six groups of 10 rodents with simulated head and neck cancer were injected with cyclic dinucleotide, hydrogel, and a control drug (collagen) without and in combination with cyclic dinucleotide or hydrogel, as well as the experimental drug STINGel. As a result, only 1 out of 10 animals of the groups that received injections of cyclic dinucleotide and its combination with collagen survived for 105 days – and 6 out of 10 animals that were injected with STINGel. Moreover, in the future, the latter demonstrated resistance to repeated implantation of malignant cells. This indicated that their immune system acquired the ability to identify and destroy not only existing tumors, but also their possible relapses.
The authors also compared the effectiveness of their hydrogel with the effectiveness of more common hydrogel variants and demonstrated their inability to ensure the gradual release of the drug, as well as an increase in its activity compared with the results of the use of cyclic dinucletide.
The cyclic dinucleotide used in the study is currently undergoing clinical trials, and the authors believe that their proposed approach will significantly expand the possibilities of using this powerful immunotherapeutic drug in the treatment of various types of tumors resistant to traditional methods of treatment.
Article by David G. Leach et al. STINGel: Controlled release of a cyclic dinucleotide for enhanced cancer immunotherapy published in the journal Biomaterials/
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on Rice News: Slow-release hydrogel aids immunotherapy for cancer.