The Breakthrough of Biosimilars: A Twist in the Narrative of Biological Therapy

Kabir, Eva Rahman; Moreino, Shannon Sherwin; Siam, Mohammad Kawsar Sharif

doi:10.3390/biom9090410

Cited by 59 publications

(64 citation statements)

References 112 publications

(128 reference statements)

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“…Условием его экономической эффективности является сочетание более низкой цены с сопоставимой терапевтической эффективностью и безо- [59]. Кроме того, биологические препараты обладают иммуногенностью, которая может быть обусловлена как действующим веществом, имеющим белковую или полипептидную структуру, так и примесями, связанными с процессом производства (остаточные белки продуцента, остаточная ДНК-продуцента, эндотоксины), что обусловливают ее крайнюю чувствительность к малейшим изменениям технологии получения препарата [60,61]. Опыт экономически развитых стран с жесткими регуляторными требованиями в целом свидетельствует о хорошем качестве воспроизведенных препаратов, позволяющем получить значительную экономию средств и их перераспределение, в т. ч. на закупку инновационных препаратов с благоприятным соотношением стои-мость/полезность [62].…”

Section: возможные пути решения экономических проблем противоопухолевunclassified

Economic challenges of oncological diseases’ pharmacotherapy

2020

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Oncological diseases rank high in the structure of population morbidity and mortality. They entail considerable direct and indirect economic costs. In the past decades, the cost of oncotherapy has increased significantly, which is largely conditioned by high prices of antitumor drugs, which on average increased by ten times in the past ten years. At the same time, many innovative medications have only minor advantages over cheaper old medications because they are registered based on the data on the achievement of the surrogate endpoint – extension of progression-free survival. The high cost of oncotherapy is associated with financial toxicity that affects negatively the patients’ quality of life, their adherence to treatment and consequently survival. To reduce the cost of oncotherapy, it is necessary to conduct pharma-economic analysis, the results of which can serve as the basis to negotiate price-cutting with the manufacturers, as well as to use high-quality generics and biosimilars as effective and safe as their originals, and to monitor effectiveness and safety of all antitumor drugs within the pharmacovigilance framework.

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Section: возможные пути решения экономических проблем противоопухолевunclassified

Economic challenges of oncological diseases’ pharmacotherapy

2020

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“…The high demand and expensiveness of antibodies have encouraged the development of biosimilar molecules produced by different hosts, which possess comparable characteristics to the already approved biopharmaceuticals [4]. Thus, these alternative antibodies are predicted to play a vital role in biomedical market in the coming years and to signi cantly boost the biological therapy by extending more options for treatment processes [5].…”

Section: Introductionmentioning

confidence: 99%

Functional production of human antibody by the filamentous fungus Aspergillus oryzae

Huynh

Morita

Sakamoto

et al. 2020

Preprint

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Background: Monoclonal antibodies (mAbs) as biopharmaceuticals take a pivotal role in the current therapeutic applications. Generally mammalian cell lines, such as those derived from Chinese hamster ovaries (CHO), are used to produce the recombinant antibody. However, there are still concerns about the high cost and the risk of pathogenic contamination when using mammalian cells. Aspergillus oryzae, a filamentous fungus recognized as a GRAS (Generally Regarded As Safe) organism, has an ability to secrete a large amount of proteins into the culture supernatant, and thus the fungus has been used as one of the cost-effective microbial hosts for heterologous protein production. Pursuing this strategy the human anti-TNFα antibody adalimumab, one of the world’s best-selling antibodies for the treatment of immune-mediated inflammatory diseases including rheumatoid arthritis, was chosen to produce the full length of mAbs by A. oryzae. Generally, N-glycosylation of the antibody affects immune effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) via binding to the Fc receptor (FcγR) on immune cells. The CRISPR/Cas9 system was used to first delete the Aooch1 gene encoding a key enzyme for the hyper-mannosylation process in fungi to investigate the binding ability of antibody with FcγRIIIa.Results: Adalimumab was expressed in A. oryzae by the fusion protein system with α-amylase AmyB. The full-length adalimumab consisting of two heavy and two light chains was successfully produced in the culture supernatants. Among the producing strains, the highest amount of antibody was obtained from the ten-protease deletion strain (39.7 mg/L). Two-step purifications by Protein A and size-exclusion chromatography were applied to obtain the high purity sample for further analysis. The antigen-binding and TNFα neutralizing activities of the adalimumab produced by A. oryzae were comparable with those of a commercial product Humira®. No apparent binding with the FcγRIIIa was detected with the recombinant adalimumab even by altering the N-glycan structure using the Aooch1 deletion strain, which suggests only a little additional activity of immune effector functions.Conclusion: These results demonstrated an alternative low-cost platform for human antibody production by using A. oryzae, possibly offering a reasonable expenditure for patient’s welfare.

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“…The high demand and expensive payment of antibodies have encouraged the development of a biosimilar produced by different hosts, which possesses comparable characteristics to the already approved biopharmaceutical [4]. Thus, biosimilar is predicted to play a vital role in biomedical market in the coming years and to significantly boost the biological therapy by extending more options for treatment processes [5].…”

Section: Introductionmentioning

confidence: 99%

Functional production of human antibody by the filamentous fungus Aspergillus oryzae

Huynh¹,

Morita²,

Sakamoto³

et al. 2020

Preprint

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Background: Monoclonal antibodies (mAbs) as one of the biopharmaceuticals take a pivotal role in the current therapeutic application. Generally, mammalian cell lines such as Chinese hamster ovary (CHO) cell lines are used to produce the recombinant antibody. However, there are still concerns about the high cost and the risk of pathogenic contamination when using mammalian cells. Aspergillus oryzae, the filamentous fungus recognized as a GRAS (Generally Regarded As Safe) organism, has an ability to secrete a large amount of proteins into the culture supernatant, and thus the fungus has been used as one of the cost-effective microbial hosts for heterologous protein production. Pursuing this strategy, human anti-TNFα antibody adalimumab, one of the world’s best-selling antibodies for the treatment of immune-mediated inflammatory diseases including rheumatoid arthritis, was chosen to attempt for producing the full length of mAbs by A. oryzae. Generally, N-glycosylation in antibody affects the immune effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) via binding to the Fc receptor (FcγR) on immune cells. The CRISPR/Cas9 system was used to firstly delete the Aooch1 encoding a key enzyme for the hyper-mannosylation process in fungi to investigate the binding ability of antibody with FcγRIIIa.Results: The adalimumab was expressed in A. oryzae by the fusion protein system with α-amylase AmyB. The full-length adalimumab consisting of two heavy and two light chains was successfully produced in the culture supernatants. Among the producing strains, the highest amount of antibody was obtained from the ten-protease deletion strain (39.7 mg/L). Two-step purifications by Protein A and size-exclusion chromatography were applied to obtain the high purity sample for further analysis. The antigen-binding and TNFα neutralizing activities of the adalimumab produced by A. oryzae were comparable with those of the commercial product – Humira. No apparent binding with the FcγRIIIa was detected with the recombinant adalimumab even by altering the N-glycan structure under the Aooch1 deletion, which suggests only a little additional activity of immune effector functions.Conclusion: These results demonstrated an alternative low-cost platform for human antibody production by using A. oryzae, possibly offering a reasonable expenditure for patient’s welfare.

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The Breakthrough of Biosimilars: A Twist in the Narrative of Biological Therapy

Cited by 59 publications

References 112 publications

Economic challenges of oncological diseases’ pharmacotherapy

Economic challenges of oncological diseases’ pharmacotherapy

Functional production of human antibody by the filamentous fungus Aspergillus oryzae

Functional production of human antibody by the filamentous fungus Aspergillus oryzae

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