The possibility of eliminating Alzheimer’s disease, cancer and other serious ailments once and for all – this work, already covering the beginnings of genetic engineering, was presented at the 15th International Congress of Immunology in Milan
During this year’s 15th International Immunology Congress in Milan, several research teams presented papers on strengthening the immune system by directing its cells to destroy cancerous tumors and fighting pathogens with which it had not been able to cope naturally. There is no doubt that the control of some functions of the immune system is an important area of research and in a few years’ time it will bring new, revolutionary therapies.
Scientists target macrophages
“If we want to increase the body’s defenses, we have to think about macrophages,” says Dr. Michele De Palma of the San Raffaele Research Institute in Italy. They, as well as neutrophils and basophils, whose functions have been poorly understood so far, are the main focus of research.
Macrophages are connective tissue cells that divide into sedentary and migratory cells. Their main task is to defend the body: phagocytosis, i.e. the absorption of pathogens, and the synthesis of various substances involved in immunological processes. The average macrophage can eat up to 100 bacteria. It works together with monocytes – the largest leukocytes, destroying dead tissue and pathogens. Macrophages also appear in inflammation and neoplasms, forming the so-called macrophages present in the tumor development environment (TAM). There are two types of TAM macrophages – M2 macrophages promote the growth of blood vessels and weaken the body’s defenses, while M1 macrophages activate cells of the immune system that attack cancerous tumors. M1 macrophages do not have the ability to intensify the growth of blood vessels, which does not favor tumor growth.
It was macrophages M1 and M2 that the team of Swedish scientists from the Karolinska Institutet, led by Prof. Robert Harris. Swedish scientists decided to investigate whether they could reduce the amount of beta-amyloid and thus reduce the symptoms of one of the most difficult to treat diseases of the 1st century – Alzheimer’s disease. Beta amyloid is an abnormal protein found in the brain of people with this disease. For several years, science has suspected that its deposits in the form of plaques and lumps called oligomers contribute to the development of the disease and cause its worst symptoms, such as memory loss, regressions, dementia, and lack of consistency of thinking. Researchers from the Karolinska Institutet used mouse models – APP / PSXNUMX transgenic mice that spontaneously develop Alzheimer’s disease to test the ability of macrophages to fight the disease.
The researchers placed M1 and M2 macrophages in the hippocampus, a site that is crucial for Alzheimer’s disease. It is a small horn-shaped structure located in the temporal lobe of the cerebral cortex. It is mainly responsible for memory. As it turned out, macrophages began to migrate towards and destroy the beta-amyloid plaques. M1 macrophages retained much better efficiency in the degradation of this harmful protein. According to the scientists, the results of the study are promising, as there is a possibility of eliminating beta amyloid deposits before they start showing negative symptoms, while macrophages destroy both plaques and oligomers, which drugs that dissolve this protein have not been able to do so far.
Hope in the fight against cancer
In turn, a team of Brazilian scientists led by prof. Maria Cristina Roque-Barreira from the Universidade de Sao Paulo conducted research aimed at transforming TAM macrophages, i.e. those found in the cancer environment, in such a way that they began to attack the tumor tissue.
The maintenance of a malignant tumor, like any other healthy tissue, depends on access to oxygen and nutrients. So cancer uses blood vessel growth factors to build vessels and provide itself with its own blood supply. In this way, M2 macrophages favor tumor growth. Brazilian scientists decided to treat macrophages with a lectin derived from the local plant Atrocarpus integrifolia, called jacalin. Lectins are proteins or glycoproteins that specifically bind certain carbohydrates without enzymes. They occur in organisms at various stages of evolutionary development (microorganisms, plants, fungi, animals) and play important functions in the life processes of these organisms. The ability of lectins, such as jacalin, to bind to precisely defined sugars in protein molecules and the reversible nature of these bonds make them excellent tools for molecular manipulation.
Brazilian researchers found that when applied to macrophages, jacalin activates the change factor, turning them into pro-inflammatory M1 macrophages that begin to destroy colon tumor tissue. Flow cytomerism studies have proven that the viability of tumor cells decreases and the process of cell death begins in them – apoptosis. Research will continue to develop a jacalin-based drug that could stimulate macrophages to destroy some cancerous tumors.
Genetic manipulations
scientists went the farthest in their research – a team led by prof. Igor Malyshev from the Moscow State Medical and Dental University named after AI Yevdokimov. scientists assumed that the immune system does not form anew in the face of a threat each time, but uses ready-made solutions. This system of interdependencies between cells creates a single, flexible network they call the immune matrix, which collects in the face of a threat and aims to eliminate it and restore balance. The interfering element is neoplastic tissue, which reprograms this matrix so that its elements turn into cancer-promoting factors. Macrophages play an important role in this transformation.
scientists decided to reprogram the matrix to create macrophages with stable properties that fight cancer tissue. The first goal of research is to block macrophage receptors so that they cannot be reprogrammed by cytokines secreted by the tumor. The effects of these works, according to prof. Malyszewo are promising. The next targets, which are clearly genetic engineering, look impressive. scientists want to create intelligent macrophages that will not only protect against the development of a cancerous tumor, but also increase the strength of the anti-cancer response in the event of cancer development. Finally, the team from MSUMD wants to embed such intelligent macrophages permanently in the immune system. It can already be said that despite the positive effects of the first experiments, these works will take about 10 years.
Tekst: Marek Mejssner