Preclinical study of monoclonal antibodies (MAT). Report 1: experimental models for the assessment of MAT in respiratory diseases

DOI: 10.29296/2618723X-2019-04-05

M.N. Makarova, ORCID 0000-0003-3176-6386,
V.G. Makarov, ORCID 0000-0002-2447-7888

«Institute of Preclinical Research» Ltd. 188663, Russia, Leningrad oblast, Vsevolozhskiy district, Kuzmolovskiy t.s., Zavodskaya st. 3-245
E-mail: [email protected]


Keywords: monoclonal antibody diseases of the respiratory system experimental model

For citation:

M. Makarova, V. Makarov Preclinical study of monoclonal antibodies (MAT). Report 1: experimental models for the assessment of MAT in respiratory diseases. Laboratory Animals for Science. 2019; 4. https://doi.org/10.29296/2618723X-2019-04-05

Abstract

Currently, there are more and more patients with lung diseases who develop resistance to corticosteroids. In this regard, the scientists drew attention to the possibility of using monoclonal antibodies (MAB) to enhance the treatment of bronchial asthma, chronic obstructive pulmonary disease (COPD) and other diseases. Studies on the use of MAT in respiratory diseases have appeared recently and are quite rare, although they have great potential in the treatment of such patients.

In-depth experimental studies on animals are needed to evaluate new MAB and introduce them into clinical practice of treatment of respiratory diseases. At the same time, models adequate to the tasks are of paramount importance. Modeling of respiratory diseases in animals is carried out by intraperitoneal or subcutaneous administration of ovalbumin followed by its intranasal administration or spraying (bronchial asthma), as well as by exposure to cigarette smoke (COPD). Doses of ovalbumin vary depending on the type of animals used from 10 mcg in mice to 10 mg in rabbits. For intranasal administration and for spraying in special chambers, 1-4% ovalbumin aerosol is used.

Most often, especially for the preliminary assessment of drugs, including MAB, when modeling respiratory diseases, wild species mice are used – C57BL/6 and BALB/c. However, to confirm the data obtained in mice, most researchers recommend using larger and closer to humans animals (Guinea pigs, rabbits, mini-pigs, monkeys). When studying the effect of MAB on the state of the respiratory tract, along with such standard routes of administration for MAB, as intravenous and subcutaneous, it is important to study the inhalation pathway.

To assess the effectiveness of the studied MAB in respiratory diseases, it is recommended to use such indicators: resistance of the bronchi and trachea, the content of eosinophils in blood and lung lavage, the content of inflammatory mediators and cytokines (CD4+ and CD25+, IL-5, TNF-α, NF-KB, NO, IL-8, IL-2, IL-6, IL-13 and others), as well as corticosterone in blood plasma, histamine in lung lavage, histological picture of the trachea and bronchi.

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