18 March 2015

About anti–cancer antibodies in the garden - first-hand

Plant factory of human antibodies

<url>The Moscow government has awarded annual prizes to young scientists.

Among the laureates are a team of employees of the Laboratory of Molecular Biology of Viruses of the A.N. Belozersky Research Institute of Physico–Chemical Biology of Moscow State University: Doctor of Biological Sciences Tatiana Komarova (who received the L'Oreal –UNESCO National Scholarship in 2012), left, and Ekaterina Sheshukova (right). The topic of the work: "Fundamental and biotechnological aspects of plant-pathogen interaction". We publish interviews with scientists.

– Who did you study with, who are your teachers and colleagues in Russia and abroad?

Tatiana Komarova: I graduated from the Faculty of Biology of Lomonosov Moscow State University, and then I completed full-time postgraduate studies. The first laboratory where I came to do my term paper and then my thesis was the laboratory of Biochemistry of plant viruses at the Department of Virology of the Faculty of Biology of Moscow State University. My first supervisor at that time was Maxim Vladimirovich Skulachev, who taught me the basic methods and techniques of molecular biology and genetic engineering.

After receiving my diploma, I decided to enter graduate school and continue my scientific activity in the same laboratory under the guidance of the head of the laboratory, Doctor of Biological Sciences, Professor Yuri Leonidovich Dorokhov. For more than 10 years I have been working in the group of Yuri Leonidovich, whom I consider my teacher and mentor, and, undoubtedly, a brilliant scientist.

Ekaterina Sheshukova: I am a graduate of the Chemical Faculty of Lomonosov Moscow State University. The laboratory where I did my thesis belongs to the Department of Nucleic Acid Chemistry of the Department of Chemistry of Natural Compounds of the Faculty of Chemistry. The first supervisor of my work was Smolov Maxim Alexandrovich, but after his departure I came under the guidance of Korolev Sergei Pavlovich, in addition, all my thesis was under the strict guidance of the head of the laboratory, Doctor of Chemical Sciences Gottikh Marina Borisovna. It was they who taught me the basic methods and techniques of biochemistry.

After graduating from the Faculty of Chemistry, I wanted to continue doing science, but I have always been attracted to molecular biology, which borders on biochemistry. Therefore, I decided to change my profile a little and came to the laboratory of biochemistry of plant viruses under the supervision of Doctor of Biological Sciences, Professor Yuri Leonidovich Dorokhov. Since the decision was made quite quickly, I did not enroll in graduate school, but became a candidate at the Faculty of Bioengineering and Bioinformatics of Moscow State University.

From the moment I got into the new laboratory, my mentor and teacher was Komarova Tatiana Valeryevna, together with whom we won the Moscow Government Prize. I have been working in this laboratory for three years now. Thanks to Tatiana and Yuri Leonidovich, I mastered the basic methods and approaches of molecular biology and became seriously interested in this discipline.

– What would you call your subdiscipline, the direction in which you are engaged? Where else (in Russia, in the world) are doing this kind of research?

Tatiana Komarova: The name of our work just reflects the essence of the direction in general that we are engaged in. If we talk about the fields of science in which we conduct research, these are molecular biology, plant physiology, as well as the interaction of plants and pathogens, plus, of course, biotechnology. Although it is impossible to draw clear boundaries between these sections, because any research concerning the study of mechanisms at the molecular level and at the level of the whole organism is complex and, often, interdisciplinary.

As for the production of full-size antibodies in a plant, in Russia we are the first and, perhaps, the only ones who have received functionally active human anticancer antibodies in a plant cell. I would like to note that we, together with colleagues from the Blokhin Russian Cancer Research Center, conducted successful preclinical trials of these drugs on animals.

– What is the essence of your research and what tasks does it solve?

Tatiana Komarova: We are engaged in fundamental research of the mechanisms that underlie the protective reactions of plants, as well as studying the possibilities of using plants as a "factory" for the production of human antibodies. Our study proved that with the help of gaseous methanol, which for a long time was considered a byproduct of plant life, that is, just garbage, plants transmit a signal to each other informing about a potential attack of pathogens.

Imagine that one of the plants is damaged. And any damage is a gateway for infections. In this case, the damaged plant begins to emit gaseous methanol, which is captured by the "neighbors in the garden" and includes protective reactions that reduce the likelihood of bacterial infection. To obtain the pharmaceutical proteins we need, we use plant bacteria and viruses as tools. And understanding the mechanisms underlying the interaction between a plant and a pathogen is an extremely important element. This is a kind of foundation that can be further used for the development of applied technologies.

– Is it possible to talk about any practical results?

Ekaterina Sheshukova: We have already registered several patents for our developments. One of them is the production of antibodies in the plant. This is an absolute innovation. We are talking about the potential application of the results of our research in the field of oncology. So far there are no similar analogues in Russia. To date, there are similar antibodies, but obtained in the animal cell system.

Tatiana Komarova: If we are talking in the context of safety, then we need to clearly understand that antibodies obtained with the help of animal cells can be contaminated with components of animal viruses and other pathogens that pose a potential danger to humans.

Ekaterina Sheshukova: But plants can cope with environmental factors themselves, so compliance with sterility or other additional conditions at the production stage is not required. Already 5-10 days after the antibody accumulation mechanism is started, you can get a ready-made drug. The plant acts as a bioreactor.

Tatiana Komarova: Even if it is purely hypothetical to assume the presence of some kind of plant virus in the antibodies synthesized in the plant, then this does not pose a threat to humans. Suffice it to recall that the tobacco mosaic virus is constantly present in the blood of smokers and it has never caused any problems.

Ekaterina Sheshukova: In many European countries, preparations based on plant antibodies are already being received. However, in Russia, with its huge agricultural complex, we are just starting to work in this direction.

– At what stage are your developments?

Tatiana Komarova: An approach has been developed to obtain vaccine anti-cancer nanoparticles based on the tobacco virus. There is also a technology for the production of three types of therapeutic antibodies in a plant cell. The first antibody "blocks" the growth of blood vessels and blood supply to the tumor and thereby suppresses its growth. The other two antibodies are directed against breast cancer.

Ekaterina Shushukova: Clinical trials take a very long time – it may take 10 years or more before the drug is introduced into the clinic. Although, a lot depends on the situation here. For example, the herbal drug ZMapp, which began to be administered to Ebola patients, practically did not pass clinical trials. But here humanity is dealing with an emergency epidemic situation. By the way, this drug is also based on antibodies synthesized in tobacco plants. In addition, clinical trials imply the presence of a certain production, for which a sufficient amount of material is needed. And in laboratory conditions, we cannot physically achieve this.

– Tell us about your laboratory.

Tatiana Komarova: Actually, our supervisor Yuri Leonidovich Dorokhov has two sites, and we work on both. The first laboratory is located on the basis of the A.N.Belozersky Research Institute of Physico-Chemical Biology at Moscow State University, and the second is located at the N. I. Vavilov Institute of General Genetics of the Russian Academy of Sciences. The fact is that we work in several areas: we study the interactions of plants with viruses and bacteria, plant communication among themselves, the production of pharmaceutical proteins in a plant cell, and we also have a project related to an animal cell, so research is conducted in two laboratories.

In addition, we also have a small greenhouse in which we grow plants. Of course, the scale of our greenhouse is not enough to produce large batches of pharmaceutical proteins in the plant. But the technology of antibody production is good because it can be put "on stream". For example, in the USA there are companies that have organized an automated "conveyor" for cultivation, infection, cleaning… Full cycle. You give them genetic constructs, they give you the final drug. A kind of outsourcing. There is such a practice in European countries.

Ekaterina Sheshukova: By now there are already several examples of drugs approved for human use, which are proteins produced in plant cells.  For example, in Israel, the production of one of the human enzymes in carrot cells has begun, a vaccine based on plant material has also been developed, which successfully prevents the development of caries. And the Japanese have generally created a veterinary drug based on strawberries, which is rubbed into the gums of dogs so that they do not develop periodontal disease. As you can see, the direction of "green" biotechnology is very promising!

– What are the most acute problems faced by young scientists today?

Tatiana Komarova: Probably financing. There are now two state foundations in Russia – RFBR and RNF, which distribute money for various studies (for representatives of social and humanitarian disciplines, the RGNF also operates - " <url>"). This is a system of grants that are distributed on a competitive basis. However, the situation with state financing is ambiguous. Last year, an RFBR grant of 500 thousand rubles was allocated for our laboratory. This is not even enough for reagents, given that we have to buy most of them abroad. On the other hand, I had a grant from the RFBR to support young teams in the amount of 3 million per year. This is more or less worthy. But nevertheless, it is almost always necessary to find additional funds, to deny yourself something. If we compare with the situation 10 years ago, the situation is noticeably better.

Ekaterina Sheshukova: I would like to add about the so-called "brain drain". I will not undertake to speak for the entire scientific community, but from my 2012 graduation, almost a third of graduates work abroad today. It's a shame. Or here is an example: you come to an international conference. Representatives of organizations from 20 countries have been announced. Who are the main speakers? That's right, our scientists who do not work in Russia. The conditions for studying science outside Russia are still much better.

– Despite the difficulties, do you plan to continue doing research?

Ekaterina Sheshukova: Our profession is special. Not many people have such an amazing job. You can look where others can't. It can be compared to a fantastic book, from which it is impossible to tear yourself away and "swallow" page after page!

Tatiana Komarova: Science is very inspiring. Yes, we have failures, mistakes happen. But we always succeed. It's never boring. Especially biology! It's not something abstract. This is who we are. And everything around is also biology. Well, how can you remain indifferent? Of course, we need to thank the Moscow Government. I am very pleased that our work on plant antibodies won the competition, this is recognition of our merits, a very significant motivation and incentive for other young scientists.

We will continue publishing materials about the award winners

Portal "Eternal youth" http://vechnayamolodost.ru18.03.2015

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