The dream of a universal cancer vaccine … we are approaching Science and technology

In recent years, the forefront of cancer research has focused not on the inside of the tumor, but on everything around it. Oncologists call this the microenvironment: a microscopic world that is still poorly understood. Tumor cells thrive by attaching to new blood vessels that feed their special growth. In many cases, bacteria accumulate around the tumor, which may be responsible for the worsening of the disease. In some cases, there are cells in the immune system that seem to be asleep. In the midst of the most deadly and difficult to treat tumors – such as those of the pancreas or brain – there are very few T-lymphocytes, the immune cell capable of locating and eliminating any external threat. It’s as if cancer wears an invisible cloak. Nine out of ten cancer deaths are due in part to this problem: when doctors find the disease, it has already spread to other organs, causing metastases.

One of the biggest challenges in oncology is the development of vaccines that bring various forces from the immune system to the battlefield of the tumor microenvironment, regardless of the organ involved. For this reason, a molecular mechanism common to all tumors must be found. What complicates matters is that cancer has been evolving with us for millions of years and uses biological mechanisms very similar to those of healthy cells. Killing him can also mean killing the patient. This difficulty means that most of the cancer vaccines currently being pursued are personalized for each patient and his or her cancer. This poses enormous economic and technical challenges: cancer is one of the most common diseases in the world, with around 18 million new cases diagnosed each year.

A new study has revived the dream of a multipurpose cancer vaccine. This includes a new molecule identified by physician and immunotherapy expert Kai Vucherpfenig of the Dana-Farber Cancer Institute in Boston, which uses a variety of tactics to eliminate the invisibility of tumors.

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

The team of David Mooney, a bioengineer at Harvard University, has designed a vaccine based on the molecule identified by his colleague at Dana-Farber, which generates antibodies against these two proteins. These molecules bind to them and prevent them from breaking down. This removes the invisible cloak of the tumor and brings to the site two types of immune cells: T cells and natural killer cells. Both are again able to identify proteins, bind to them and destroy tumor cells where they are present.

The researchers demonstrated that the vaccine was effective, with successful results in experiments with mice, and also observed that monkeys produced an adequate immune response. This immunization remains even in cases of advanced tumors that have metastasized in animals.

“This vaccine can 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, after injection, function as a hub for tens of thousands of immune system cells capable of generating antibodies against tumor proteins and stimulating other effective ones, especially T- lymphocytes and natural killers.

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

Developing effective cancer drugs is a difficult endeavor. Only three out of every 100 new drugs of this type manage to pass all clinical trials and reach the market. Success rates are even lower in the fight against more complex tumors. However, along with other approaches, this vaccine aims to act as a new weapon in the fight against cancer, along with already approved treatments.

“This study is part of a new approach to immunotherapy,” explains Ignacio Melero, an immunologist at the Center for Applied Medical Research at the University of Navarre. “The idea is to immunize so that autoantibodies are formed against the mechanisms used by the tumor to avoid the immune system’s response, so that in vaccinated patients the effectiveness of immunotherapeutic treatments can be increased. A similar approach with another type of vaccine has achieved promising results against melanoma, “Melero said.

This refers to the first clinical trials in patients with an experimental vaccine based on a small protein called IO103, which stimulates the reactive capacity of T-lymphocytes and is used in combination with checkpoint inhibitors, a type of immunotherapy against cancer that has already been approved. “We have to wait to see the results of the clinical trials, but the results so far suggest that they are facing a challenge,” Melero added.

Pedro Romero, co-director of the Ludwig Institute for Cancer Research in Switzerland, summed up the difficulty of developing non-personalized vaccines. “Cancer is not a single disease unit; there may be more than 700 different cancers that are determined by distinctive molecular profiles. All effective anti-cancer treatments are successful only against a limited number of these cancer subtypes. Nothing different can be expected from future cancer vaccines. It is possible that some immunizations, such as the one discovered by the Dana-Farber group, work against a significant group of tumors, which would be an important achievement. The biomarker in this case would be the level of MICA and MICB molecules in the blood, “he said.

Romero is optimistic about the potential of these therapeutic vaccines. “It is possible to use a combination of the two types of vaccines, semi-universal and custom. There will be potentially useful synergies for the treatment of patients. Immunotherapy for cancer is in its infancy, reaching adolescence. “Expectations are high,” he concluded.

Leave a Comment

Your email address will not be published.