A new technology developed by researchers at the University of Zurich enables the body to produce therapeutic agents on demand in the exact place where they are needed. This innovation, for example, could be extremely useful in reducing the side effects of cancer therapies . And, in addition, it could become a solution for better delivery of COVID-19-related therapies directly to the lungs .
Scientists have modified adenovirus , a common respiratory virus, to act as a kind of Trojan horse to deliver genes for cancer therapies directly into tumor cells.
Unlike other therapies, such as chemotherapy or radiation therapy, this method would not harm normal healthy cells . In turn, once inside the tumor cells, the administered genes would serve as a model for the therapeutic antibodies, cytokines and other signaling substances , which are produced by the cancer cells themselves, in such a way that they would act to eliminate the tumors inside. outward .
To achieve this, the scientists tricked the tumor into eliminating itself by producing a series of anticancer agents, but by its own cells.
Therapeutic agents, such as signaling substances or therapeutic antibodies, tend to remain, for the most part, where they are needed in the body, and do not spread through the bloodstream, where they could damage tissues and healthy organs.
Large number of drugs in tumor, low concentration in other tissues
With this system, which the scientists have baptized with the name of SHREAD, they managed to make the cancerous tumor itself produce a clinically approved antibody against breast cancer in the breast of a mouse.
After a few days, they discovered that SHREAD had produced a greater amount of antibodies in the tumor than when the drug was injected directly.
But its beneficial effects did not stop there. And, in addition, the concentration in the bloodstream and in other healthy tissues where side effects could occur was significantly better after using this method.
In order to create pores in the tumor’s blood vessels and destroy tumor cells from within the tumor, the researchers used a highly sophisticated high-resolution 3D imaging method as well as fully transparent tissues to show how the therapeutic antibody worked.
It would also be useful to combat COVID-19
As the scientists have stated, SHREAD would also be applicable not only in the fight against breast cancer. Since different healthy tissues no longer come into contact with significant levels of the therapeutic agent, it would also be applicable for the administration of a very wide range of so-called biologics , which consist of potent protein-based drugs that otherwise do. they would be too toxic.
The researchers are currently applying their technology in a project aimed at becoming a therapy for COVID-19. In fact, adenoviral vectors are already being used in different COVID vaccines, such as Johnson & Johson or AstraZeneca.
In this sense, when administering the SHREAD treatment to patients through an inhaled aerosol, the treatment would mainly target the production of COVID antibodies in lung cells, where they are most needed. This would help reduce costs, increase the accessibility of COVID therapies and, in turn, improve the delivery of vaccines by inhalation.
Reference: “The SHREAD gene therapy platform for paracrine delivery improves tumor localization and intratumoral effects of a clinical antibody” by Sheena N. Smith, Rajib Schubert, Branko Simic, Dominik Brücher, Markus Schmid, Niels Kirk, Patrick C. Freitag, Viviana Gradinaru and Andreas Plückthun, May 17, 2021, Proceedings of the National Academy of Sciences. DOI: 10.1073 / pnas.2017925118
