A study about the dream of a universal vaccine against cancer | Science | The USA Print


For some years now, the frontier of cancer research has not been inside the tumor, but in everything that surrounds it. Oncologists call it the microenvironment: a microscopic world that is still poorly understood. Tumor cells advance by laying out new blood vessels to feed their aberrant growth. In many cases, bacteria congregate around the tumor and may be influencing the disease. Sometimes there are also cells of the immune system that seem to be asleep. In the environment of the most lethal and difficult to treat tumors – such as those of the pancreas or brain – there are hardly any T lymphocytes, the type of immune cell capable of locating and annihilating any external threat. It is as if cancer is wearing an invisibility cloak. Nine out of ten cancer deaths are due in part to this problem: when doctors detect the disease, it has already spread to other organs causing metastasis.

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

A study has revived the dream of a polyvalent cancer vaccine. It is a new molecule identified by the doctor and expert in immunotherapy Kai Wucherpfennigof the Dana-Farber Cancer Institute in Boston, using 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.

The team of 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. That removes the tumor’s invisibility cloak and brings two types of immune cells to the site: T cells and natural killer cells. Both are again able to identify the proteins, bind to them and destroy 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 metastasized 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 spent years developing vaccines based on three-dimensional microscopic structures that, once injected, function as a headquarters which is attended by tens of thousands of cells of the immune system capable of generating antibodies against tumor proteins and stimulating other effective ones, especially T lymphocytes and natural killers.

This new prototype cancer vaccine has been published in Nature, reference of world science. One of the most outstanding characteristics is that it disables one of the mechanisms of invisibility before 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 types of tumor”, summarizes Wucherpfennig. The team plans to start 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 the most complicated tumors to fight. 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, an immunologist at the University of Navarra’s Center for Applied Medicine Research. “The idea is to immunize so that autoantibodies are formed against mechanisms used by the tumor 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 little protein called IO103 that stimulates the reaction capacity of T lymphocytes and that is administered together with checkpoint inhibitors, a type of immunotherapy against cancer that has already been approved. “We have to wait to see what the clinical trials hold, but the results so far suggest that they can stand up,” adds Melero.

Peter Romero, co-director of the Ludwig Institute for Cancer Research in Switzerland, sums up the difficulty of achieving non-personalized vaccines. “Cancer is not a uniform disease entity; instead 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. Nothing different can be expected from future cancer vaccines. It is possible that some immunizations like the one discovered by this group at Dana-Farber work against an important group of tumors, which would be an important achievement. The biomarker in this case would be the level of the MICA and MICB molecules in the blood”, 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.

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