Delivering cancer vaccines to the heart of immune cells
In the fight against cancer, researchers have turned to vaccines that stimulate the immune system to identify and destroy tumor cells. NCCR Bio-Inspired Materials scientists have developed artificial spider silk microcapsules that could boost the potency of these vaccines.
Cancer treatment vaccines, also called therapeutic vaccines, are designed to boost the body's natural defenses to fight the disease. The desired immune response, however, is not always guaranteed. In order to strengthen the efficacy of these vaccines – in particular on T lymphocytes, which are specialized in the detection of cancer cells – NCCR Bio-Inspired Materials researchers from the universities of Geneva and Fribourg, as well colleagues from Munich and Bayreuth, in collaboration with the German company AMSilk, have developed artificial spider silk microcapsules capable of delivering a vaccine directly to immune cells.
The human immune system is largely based on two types of cells: B lymphocytes, which produce the antibodies needed to defend against various infections, and T lymphocytes. When it comes to cancer and certain infectious diseases such as tuberculosis, T lymphocytes must be stimulated in order to take action. However, their activation mechanism is more complex than that of B lymphocytes: to trigger a response, it is necessary to use a peptide, a small piece of protein that, if injected alone, is rapidly degraded by the body even before reaching its target.
“To develop immunotherapeutic drugs effective against cancer, it is essential to generate a significant response of T lymphocytes,” says NCCR Principal Investigator Professor Carole Bourquin, a specialist in antitumor immunotherapies at the University of Geneva’s faculties of medicine and science, who directed this project. “As the current vaccines only have a limited influence on T-cells, it is crucial to develop other vaccination procedures.”
The researchers chose to use synthetic spider silk biopolymers – a lightweight, biocompatible, non-toxic material that is highly resistant to degradation from light and heat. “We recreated this special silk in the lab to insert a peptide with vaccine properties,” explains Professor Thomas Scheibel, a spider silk specialist from the University of Bayreuth who participated in the study. “The resulting protein chains are then salted out to form injectable microparticles.”
Silk microparticles form a transport capsule that protects the vaccine peptide from rapid degradation and delivers the peptide to the center of the lymph node cells, thereby considerably boosting T lymphocyte immune responses. “Our study has proved the validity of our technique,” reveals Bourquin, who was an NCCR Bio-Inspired Materials Principal Investigator until the end of May 2018. “We have demonstrated the effectiveness of a new vaccination strategy that is extremely stable, easy to manufacture, and easily customizable.”
The synthetic silk biopolymer particles demonstrate a high resistance to heat, withstanding over 100°C for several hours without damage. In theory, this process would make it possible to develop vaccines that do not require adjuvants and cold chains – an undeniable advantage, especially in developing countries where the preservation of vaccines can be of great difficulty. One of the limitations of this process, however, is the size of the microparticles: while the concept is in principle applicable to any peptide, as these are all small enough to be incorporated into silk proteins, further research is needed to see if it is also possible to incorporate the larger antigens used in standard vaccines, especially in those against viral diseases.
The properties of spider silk make it a particularly interesting product: it is biocompatible, solid, thin, biodegradable, resistant to extreme conditions, and even antibacterial. A wide variety of applications, including wound dressings or sutures, may be possible. The process developed by the NCCR researchers and their colleagues could also be applied to preventive vaccines to protect against infectious diseases, and constitutes an important step towards vaccines that are stable, easy to use, and resistant to the most extreme storage conditions.
Reference: Lucke, M.; Mottas, I.; Herbst, T.; Hotz, C.; Römer, L.; Schierling, M.; Herold, H.M.; Slotta, U.; Spinetti, T.; Scheibel, T.; Winter, G.; Bourquin, C.; Engert, J. Engineered hybrid spider silk particles as delivery system for peptide vaccines, Biomaterials, 2018, 172, 105