How mRNA Vaccine Eradicates Pancreatic Cancer

Messenger RNA (mRNA) vaccines may be the hottest thing in science now, as they helped turn the tide against COVID-19. But even before the pandemic began, Memorial Sloan Kettering Cancer Center researchers had already been working to use mRNA vaccine technology to treat cancerVinod Balachandran a physician-scientist affiliated with the David M. Rubenstein Center for Pancreatic Cancer Research and the Parker Institute for Cancer Immunotherapy, is leading the only clinical trial to test mRNA vaccines for pancreatic cancer. The key to these vaccines appears to be proteins in the pancreatic tumors, called neoantigens, which alert the immune system to keep the cancer at bay.

The vaccines are custom-made for every person. The hope is that the vaccine will stimulate the production of certain immune cells, called T cells, that recognize pancreatic cancer cells. This could reduce the risk of the cancer returning after the main tumor was removed by surgeryIn 8 of 16 patients studied, the vaccines activated T cells that recognize the patient’s own pancreatic cancers. These patients also showed delayed recurrence of their pancreatic cancers, suggesting the T cells activated by the vaccines may be having the desired effect to keep pancreatic cancers in check

There has been great interest in using immunotherapy for pancreatic cancer because nothing else has worked very well. We thought immunotherapy held promise because of research we began about seven years ago. A small subset of patients with pancreatic cancer manage to beat the odds and survive after their tumor is removed. We looked at the tumors taken from these select patients and saw that the tumors had an especially large number of immune cells in them, especially T cells. Something in the tumor cells seemed to be sending out a signal that alerted the T cells and drew them in.

Source: https://www.thebrighterside.news/

Personalized cancer vaccines

Therapeutic cancer vaccines were first developed 100 years ago and have remained broadly ineffective to date. Before tangible results can be achieved, two major obstacles must be overcome. Firstly, since tumor mutations are unique to each patient, cancer cell antigens must be targeted extremely precisely, which is very hard to achieve. Secondly, a safe system is needed to deliver the vaccine to the right location and achieve a strong and specific immune response.

Li Tang’s team at EPFL’s School of Engineering in Switzerland is coming up with a solution to the delivery problem. The researchers have used a polymerization technique called polycondensation to develop a prototype vaccine that can travel automatically to the desired location and activate immune cells there. The patented technique has been successfully tested in mice and is the topic of a paper appearing in ACS Central Science. Li Tang has also co-founded a startup called PepGene, with partners that are working on an algorithm for quickly and accurately predicting mutated tumor antigens. Together, the two techniques should result in a new and better cancer vaccine in the next several years.

Helping the body to defend itself

Most vaccines – against measles and tetanus for example – are preventive. Healthy individuals are inoculated with weakened or inactivated parts of a virus, which prompt their immune systems to produce antibodies. This prepares the body to defend itself against future infection.

However, the aim of a therapeutic cancer vaccine is not to prevent the disease, but to help the body defend itself against a disease that is already present. “There are various sorts of immunotherapies other than vaccines, but some patients don’t respond well to them. The vaccine could be combined with those immunotherapies to obtain the best possible immune response,” explains Li Tang. Another advantage is that vaccines should reduce the risk of relapse.

Delivering a cancer vaccine to the immune system involves various stages. First, the patient is inoculated with the vaccine subcutaneously. The vaccine will thus travel to the lymph nodes, where there are lots of immune cells. Once there, the vaccine is expected to penetrate dendritic cells, which act as a kind of alert mechanism. If the vaccine stimulates them correctly, the dendritic cells present specific antigens to cancer-fighting T-cells, a process that activates and trains the T-cells to attack them.

The procedure appears simple, but is extremely hard to put into practice. Because they are very small, the components of a vaccine tend to disperse or be absorbed in the blood stream before reaching the lymph nodes.

To overcome that obstacle, Li Tang has developed a system that chemically binds the vaccine’s parts together to form a larger entity. The new vaccine, named Polycondensate Neoepitope (PNE), consists of neoantigens (mutated antigens specific to the tumor to be attacked) and an adjuvant. When combined within a solvent, the components naturally bind together, forming an entity that is too large to be absorbed by blood vessels and that travels naturally to the lymph nodes.

Source: https://actu.epfl.ch/news/