The topic is covered in practically all its aspects in the book Animal cell technology: from biopharmaceuticals to gene therapy, from Editora Taylor & Francis, which will have its Portuguese edition launched soon by Editora Roca. “The book has 21 chapters, written by 43 authors from nine countries, in more than 500 pages”, says Ângela Maria Moraes, professor at the Faculty of Chemical Engineering (FEQ) at Unicamp and one of the organizers of the work.
Professor Octavio Ramírez, from the National Autonomous University of Mexico, informs in the preface that among the more than 500 biopharmaceutical products that are currently in clinical trials, around half are produced using the cultivation of animal cells. According to him, biopharmaceuticals obtained through this technology represent a market worth tens of billions of dollars annually and growing sharply.
“The book is divided into two parts, one with fundamentals and the other focused on applications in the cultivation of animal cells”, explains Ângela Moraes. The 21 chapters are related to the most relevant biological aspects – cloning and expression of heterologous proteins, cell growth and death, culture media and metabolism – and also with technological and engineering aspects – design, operation, monitoring and control of bioreactors, in addition to cell separation and product purification.
According to the FEQ professor, the book initially records the milestones in the cultivation of animal cells, which seek to produce biopharmaceuticals on a larger scale. “The development of special flasks for the cultivation of these cells, with lids that facilitate oxygenation and in suitable formats to promote cell adhesion and storage in an oven, already represents a milestone.”
Another milestone, in Ângela Moraes' opinion, was the introduction of antibiotics into the culture medium, in the middle of the last century, in order to overcome problems with microbial contamination. “An animal cell takes an average of 24 hours to duplicate itself, while a bacteria can do it in 20 minutes, dominating the system.”
After detailing the characteristics of animal cells in culture and comparing their cultivation with that of microorganisms, the authors deal with the cloning of animal cells for the production of heterologous proteins. “Methodologies are presented to genetically modify cells to obtain a protein of interest. It is also described how to isolate a cell or how to look for those of interest among the modified population”.
Hybridomas – The book details the fundamentals of hybridoma technology, fusion products vitro of myelomas with normal B lymphocytes. “A lymphocyte producing an antibody of interest, for example, is not capable of propagating vitro, whereas myelomas can be cultured indefinitely. The hybridoma combines the positive characteristics of both: it reproduces countless times and can 'eternally' supply the desired molecule.”
There is a chapter entirely dedicated to the formulation of culture media for animal cells, with emphasis on those free of animal serum. “With the advent of 'mad cow' disease and the transfer of other contaminants, such as viruses, along with this type of serum, regulatory agencies began to require culture media that were more chemically defined and free from components of animal origin.”
The book describes the mechanism of cell proliferation vitro, with special attention to cell death, which needs to occur as late as possible in order to extend the production period. “A chapter that is of particular interest to chemical engineers is the mathematical modeling of cell growth and product synthesis.”
Purification – Protein purification techniques, according to Ângela Moraes, are also among the important information in the work, as a purity of up to 99,9% is often required for therapeutic proteins. In addition to procedures related to purification, the book also deals with regulatory, quality control and validation aspects.
Intellectual property is also the subject of the book, aimed mainly at academic researchers, who are sometimes more concerned with publishing the results of their work in scientific journals than with patenting products. “We explain the patentability requirements and point out the paths, in addition to showing examples of inventions”.
Still in this regard, the professor mentions recombinant proteins and viral vaccines, among other products, currently available and which have a guaranteed market. “We tell the story of the development of some of them, their current commercialization and we also inform about expired and soon-to-expire patents – which would allow them to be produced in Brazil. One example is erythropoietin, used in anemia therapy, which has already motivated Argentina to install a plant for its production.”
Biopesticides – Biopesticities have their place in the book. Ângela Moraes notes that we hear little about these products, although Brazil is one of the biggest users, especially in soybean cultivation. “To control the soybean caterpillar, which defoliates the crop in a short period of time, baculoviruses, commonly obtained from infected caterpillars, can be used.”
The professor informs that the baculovirus is very specific, harmless to mammals and has low persistence in the environment. However, the lack of information contributes to the predominance of chemical pesticides, with their known harm to health and nature. “The biopesticide infects the caterpillar, which becomes ill and takes a few days to die. As the process is slower, the farmer sometimes questions its effectiveness.”
The professor adds that the country also lacks a better defined platform for large-scale baculovirus production, which could be done by infecting insect cells in culture, as opposed to using caterpillars, increasing the supply of viruses.
The last two chapters of the book involve two highly fashionable areas in terms of application: the cultivation of stem cells for use in various therapies, in an article written by renowned experts; and gene therapy, where the possibilities for cultivating animal cells are commented by authors of the same level. “Knowledge in these areas is still limited, but the potential of this technology for these two types of therapy is spectacular”, assures Ângela Moraes.
Portuguese edition meets student requests
A network of Brazilian researchers involved in the cultivation of animal cells began to emerge a few years ago, gathered around training courses organized by professor Leda Castilho, from the Federal University of Rio de Janeiro (UFRJ). In 2004, the professor organized with professor Ricardo Medronho, also from UFRJ, the XNUMXst Latin American Seminar on Cell Cultivations, which attracted researchers from abroad to the network.
Active in the network, professor Ângela Moraes, together with Leda Castilho and researcher Elisabeth Augusto, from the Institute of Technological Research of the State of São Paulo (IPT), had no difficulty in responding to the request from Unicamp students, bringing together authors to produce a most complete book on this technology, in Portuguese.
This first edition in English is due to the fact that the proposal for the book and its content, which began to be produced in Portuguese in 2004, were discussed with professor Michael Butler (from the University of Manitoba, Canada), a world reference on the subject . “He, who was already listed as the author of one of the chapters, thought the idea was excellent and offered to help launch it in English, reviewing the texts and carrying out a careful analysis of the chapters' consistency. The professor came to Brazil, worked on the book for about a month and ended up co-authoring another chapter.”
The book in Portuguese is in the final proof verification phase and will be released by the middle of the year, and is aimed at undergraduates, postgraduates and researchers in bioprocess engineering, chemical engineering, pharmacy, biology, microbiology, chemistry, biomedicine and other areas related. The authors of the book's chapters in Portuguese are from Brazil, Argentina, Chile, Germany, Canada, Cuba, Uruguay, Spain and Portugal.
INFORMATION
Animal Cell Technology: From Biopharmaceuticals to Gene Therapy
Organizers: Leda R. Castilho (UFRJ), Ângela Maria Moraes (Unicamp), Elisabeth FP Augusto (IPT), Michael Butler (University of Manitoba, Canada)
Ano: 2008
Publishing company: Taylor & Francis Group
ISBN: 978-0-415-42304-5
O development of biopharmaceuticals from molecules composed of complex proteins, obtained from the cultivation of animal cells, is an area that has been undergoing a tree in the last decades. This cultivation technique, which is already used successfully in the production of vaccines and therapeutic proteins, is beginning to extend to other fields, such as organ transplants, cell and gene therapies, in vitro toxicology and physiology, production of biopesticides, devices bioelectromechanical and nanobiotechnology.
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