Preclinical Studies into Specific Toxicity of a Candidate Drug Based on Complement C3 neodeterminant Recombinant Humanized Antibody for Treating Traumatic Brain Injuries
https://doi.org/10.33647/2074-5982-17-4-68-80
Abstract
This study aims to assess the specific toxicity (allergenicity, immunotoxicity and reproduction toxicity) of a dosage form of complement C3 neodeterminant recombinant humanized antibody. The reactions of general anaphylaxis, active cutaneous anaphylaxis and delayed-type reaction demonstrated no drug-related signs of experimental animal sensitization and immediate or delayed hypersensitivity in the treated animals. It was found that, in doses exceeding significantly the expected human therapeutic dose, the drug has no effect on humoral and cell-mediated immune responses. In addition, the drug does not suppress the phagocytic cell activity thereby indicating the absence of immunotoxic effect. Moreover, the drug has no adverse effects on male and female reproduction, progeny embryonal development, as well as prenatal and postnatal progeny development. The obtained data can be used in future clinical studies of the drug safety.
Keywords
recombinant antibody,
С3 component of the complement,
preclinical studies,
allergenicity,
immunotoxicity,
reproduction toxicity
Supporting agencies: The study was carried out under State contract No. 14.N08.11.0121 dated September 30, 2016 “Preclinical studies of a drug based on a recombinant humanized antibody to the C3 component of human complement for the treatment of traumatic brain injury” within the framework of the Federal target program “Development of pharmaceutical and medical industry of the Russian Federation for the period up to 2020 and beyond”.
About the Authors
K. A. Nekrasova
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Kseniya A. Nekrasova
197110, Saint Petersburg, Pudozskaya Str., 7
A. V. Trofimov
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Alexandr V. Trofimov
197110, Saint Petersburg, Pudozskaya Str., 7
A. V. Zhahov
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Alexandr V. Zhahov
197110, Saint Petersburg, Pudozskaya Str., 7
S. V. Rodin
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Sergey V. Rodin
197110, Saint Petersburg, Pudozskaya Str., 7
N. P. Gorbunov
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Niklay P. Gorbunov
197110, Saint Petersburg, Pudozskaya Str., 7
A. V. Petrov
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Alexandr V. Petrov, Cand. Sci. (Med.)
197110, Saint Petersburg, Pudozskaya Str., 7
N. V. Pigareva
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Nataliya V. Pigareva, Cand. Sci. (Med.)
197110, Saint Petersburg, Pudozskaya Str., 7
G. V. Alexandrov
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Georgiy V. Alexandrov, Cand. Sci. (Biol.)
197110, Saint Petersburg, Pudozskaya Str., 7
M. S. Zakharov
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Mikhail S. Zakharov
197110, Saint Petersburg, Pudozskaya Str., 7
A. S. Kiryanova
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Аnna S. Kiryanova
197110, Saint Petersburg, Pudozskaya Str., 7
O. E. Khuttunen
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Оlga E. Khuttunen
197110, Saint Petersburg, Pudozskaya Str., 7
I. V. Bendt
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Irina V. Bendt
197110, Saint Petersburg, Pudozskaya Str., 7
A. E. Krylova
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Anna E. Krylova
197110, Saint Petersburg, Pudozskaya Str., 7
A. M. Ischenko
State Research Institute of Highly Pure Biopreparations of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Alexandr M. Ischenko, Cand. Sci. (Biol.)
197110, Saint Petersburg, Pudozskaya Str., 7
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Review
For citations:
Nekrasova K.A., Trofimov A.V., Zhahov A.V., Rodin S.V., Gorbunov N.P., Petrov A.V., Pigareva N.V., Alexandrov G.V., Zakharov M.S., Kiryanova A.S., Khuttunen O.E., Bendt I.V., Krylova A.E., Ischenko A.M. Preclinical Studies into Specific Toxicity of a Candidate Drug Based on Complement C3 neodeterminant Recombinant Humanized Antibody for Treating Traumatic Brain Injuries. Journal Biomed. 2021;17(4):68-80. (In Russ.) https://doi.org/10.33647/2074-5982-17-4-68-80
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