A study brings the dream of a universal cancer vaccine closer

One of the biggest challenges in oncology is get vaccines that summon many different forces of the immune system to the battlefield of the tumor microenvironment regardless of which organ it is in. To do this, a molecular mechanism common to all these tumors must be found. The problem is that cancer takes millions of years evolving with us and uses biological mechanisms very similar to those of healthy cells. Killing him may also mean killing the patient. This difficulty has made most cancer vaccines currently being pursued personalized for each patient and their cancer. This poses enormous economic and technical challenges: cancer is one of the most prevalent diseases in the world with around 18 million new cases diagnosed each year.

A study has revived the dream of a multivalent cancer vaccine. This is a new molecule identified by the doctor and expert in immunotherapy Kai Wucherpfennig, from the Dana-Farber Cancer Institute in Boston, which uses a new tactic to strip tumors of their invisibility.

Cancer damages the DNA of cells and in response to that damage, two proteins called MICA and MICB are produced. Under normal conditions they would serve to alert the immune system, but cancer has developed the ability to cut and dilute them, which makes it invisible to the body's defenses.

- David Mooney, a bioengineer at Harvard University, designed a vaccine based on the molecule identified by his Dana-Farber colleague that generates antibodies against these two proteins. These molecules bind to them and prevent them from being cut. This removes the tumor's invisibility layer and causes two types of immune cells to come to the scene: T lymphocytes and natural killer cells. Both are once again capable of identifying proteins, binding to them and destroying the tumor cells where they are present.

Scientists have shown that the vaccine is effective in several experiments with mice and have also observed that it generates an adequate immune response in monkeys. This immunization works even in cases of advanced tumors that have caused metastasis in animals.

“This vaccine could help many patients with different types of cancer because it does not depend on the specific mutations in each patient's cancer,” explains bioengineer Mooney. His team has been developing vaccines based on microscopic three-dimensional structures for years that, once injected, work like a headquarters to which tens of thousands of immune system cells go, capable of generating antibodies against tumor proteins and stimulate other troops, especially T lymphocytes and natural killers.

This new prototype of a cancer vaccine has been published in Nature, a reference for world science. One of the most notable features is that it disables one of the mechanisms of invisibility to the immune system most used by many types of tumors, including those of the pancreas and brain glioblastoma. “The main message is that it is possible to develop vaccines that work in many patients and in different tumor types,” summarizes Wucherpfennig. The team plans to begin clinical trials with patients next year.

The development of effective drugs against cancer is a very complex task. Only three out of every 100 new drugs of this type they manage to pass all the tests in patients and reach the market. The success rate is lower with tumors that are more complicated to combat. However, this and other approaches seek to add a new weapon to the already approved treatments.

“This study is part of a new approach to immunotherapy,” explains Ignacio Melero, immunologist at the Applied Medicine Research Center of the University of Navarra. “The idea is to immunize so that autoantibodies are formed against mechanisms that the tumor uses to evade the response of the immune system, so that in vaccinated patients the effectiveness of immunotherapy treatments is enhanced. A similar approach with another type of vaccine has achieved promising results against melanoma,” highlights Melero.

It refers to the first clinical trials in patients with an experimental vaccine based on a small protein called IO103 that stimulates the reaction capacity of T lymphocytes and is administered together with checkpoint inhibitors, a type of cancer immunotherapy already approved. “We have to wait to see what the clinical trials bring, but the results so far suggest that they can stand,” adds Melero.

Pedro Romero, co-director of the Ludwig Institute for Cancer Research in Switzerland, summarizes the difficulty of obtaining non-personalized vaccines. “Cancer is not a uniform pathological entity; but there may be more than 700 different ones that are defined by distinctive molecular profiles. All effective anticancer treatments are effective against a limited number of these cancer subtypes. You cannot expect anything different from future cancer vaccines. It is possible that some immunizations like the one discovered by this Dana-Farber group work against an important group of tumors, which would be an important achievement. The biomarker in this case would be the blood level of the MICA and MICB molecules,” he details.

Romero is optimistic about the potential of these therapeutic vaccines. “It is conceivable to use a combination of the two types of vaccines, semi-universal and personalized. There would be potentially beneficial synergies for the treatment of patients. Cancer immunotherapy is in its infancy, reaching adolescence. The promise is enormous"He concludes.