Nonclinical safety, tolerance and pharmacodynamics evaluation for meplazumab treating chloroquine-resistant Plasmodium falciparum
Meplazumab is an anti-CD147 humanized IgG2 antibody. The purpose of this study was to characterize the nonclinical safety, tolerance and efficacy evaluation of meplazumab treating chloroquine resistant Plasmodium falciparum. Meplazumab was well tolerated in repeat-dose toxicology studies in cynomolg...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383520306213 |
| _version_ | 1828901894862405632 |
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| author | Kun Zhang Yu Zhao Zheng Zhang Mengyao Zhang Xiaodong Wu Huijie Bian Ping Zhu Zhinan Chen |
| author_facet | Kun Zhang Yu Zhao Zheng Zhang Mengyao Zhang Xiaodong Wu Huijie Bian Ping Zhu Zhinan Chen |
| author_sort | Kun Zhang |
| collection | DOAJ |
| description | Meplazumab is an anti-CD147 humanized IgG2 antibody. The purpose of this study was to characterize the nonclinical safety, tolerance and efficacy evaluation of meplazumab treating chloroquine resistant Plasmodium falciparum. Meplazumab was well tolerated in repeat-dose toxicology studies in cynomolgus monkeys. No observed adverse effect level was 12 mg/kg. No difference between genders in the primary toxicokinetic parameters after repeat intravenous injection of meplazumab. No increased levels of drug exposure and drug accumulation were observed in different gender and dose groups. Meplazumab had a low cross-reactivity rate in various tissues and did not cause hemolysis or aggregation of red blood cells. The biodistribution and excretion results indicated that meplazumab was mainly distributed in the plasma, whole blood, and hemocytes, and excreted in the urine. Moreover, meplazumab effectively inhibited the parasites from invading erythrocytes in humanized mice in a time-dependent manner and the efficacy is superior to that of chloroquine. All these studies suggested that meplazumab is safe and well tolerated in cynomolgus monkeys, and effectively inhibits P. falciparum from invading into human red blood cells. These nonclinical data facilitated the initiation of an ongoing clinical trial of meplazumab for antimalarial therapy. |
| first_indexed | 2024-12-13T16:07:05Z |
| format | Article |
| id | doaj.art-81b421aaefdf45e28131becb6bd3b7af |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-13T16:07:05Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-81b421aaefdf45e28131becb6bd3b7af2022-12-21T23:39:01ZengElsevierActa Pharmaceutica Sinica B2211-38352020-09-0110916801693Nonclinical safety, tolerance and pharmacodynamics evaluation for meplazumab treating chloroquine-resistant Plasmodium falciparumKun Zhang0Yu Zhao1Zheng Zhang2Mengyao Zhang3Xiaodong Wu4Huijie Bian5Ping Zhu6Zhinan Chen7College of Life Science and Bioengineering, School of Science, Beijing Jiaotong University, Beijing 100044, China; National Translational Science Center for Molecular Medicine & Department of Cell Biology, the Fourth Military Medical University, Xi'an 710032, ChinaNational Translational Science Center for Molecular Medicine & Department of Cell Biology, the Fourth Military Medical University, Xi'an 710032, ChinaNational Translational Science Center for Molecular Medicine & Department of Cell Biology, the Fourth Military Medical University, Xi'an 710032, ChinaNational Translational Science Center for Molecular Medicine & Department of Cell Biology, the Fourth Military Medical University, Xi'an 710032, China; Beijing Institute of Biotechnology, Beijing 100071, ChinaNational Translational Science Center for Molecular Medicine & Department of Cell Biology, the Fourth Military Medical University, Xi'an 710032, China; Center of Anesthesiology & Operation, Chinese PLA General Hospital, Beijing 100853, ChinaNational Translational Science Center for Molecular Medicine & Department of Cell Biology, the Fourth Military Medical University, Xi'an 710032, China; Corresponding authors. Tel: +86 29 84773863.Department of Clinical Immunology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China; Corresponding authors. Tel: +86 29 84773863.College of Life Science and Bioengineering, School of Science, Beijing Jiaotong University, Beijing 100044, China; National Translational Science Center for Molecular Medicine & Department of Cell Biology, the Fourth Military Medical University, Xi'an 710032, China; Corresponding authors. Tel: +86 29 84773863.Meplazumab is an anti-CD147 humanized IgG2 antibody. The purpose of this study was to characterize the nonclinical safety, tolerance and efficacy evaluation of meplazumab treating chloroquine resistant Plasmodium falciparum. Meplazumab was well tolerated in repeat-dose toxicology studies in cynomolgus monkeys. No observed adverse effect level was 12 mg/kg. No difference between genders in the primary toxicokinetic parameters after repeat intravenous injection of meplazumab. No increased levels of drug exposure and drug accumulation were observed in different gender and dose groups. Meplazumab had a low cross-reactivity rate in various tissues and did not cause hemolysis or aggregation of red blood cells. The biodistribution and excretion results indicated that meplazumab was mainly distributed in the plasma, whole blood, and hemocytes, and excreted in the urine. Moreover, meplazumab effectively inhibited the parasites from invading erythrocytes in humanized mice in a time-dependent manner and the efficacy is superior to that of chloroquine. All these studies suggested that meplazumab is safe and well tolerated in cynomolgus monkeys, and effectively inhibits P. falciparum from invading into human red blood cells. These nonclinical data facilitated the initiation of an ongoing clinical trial of meplazumab for antimalarial therapy.http://www.sciencedirect.com/science/article/pii/S2211383520306213MeplazumabCD147SafetyToleranceEfficacyNonclinical |
| spellingShingle | Kun Zhang Yu Zhao Zheng Zhang Mengyao Zhang Xiaodong Wu Huijie Bian Ping Zhu Zhinan Chen Nonclinical safety, tolerance and pharmacodynamics evaluation for meplazumab treating chloroquine-resistant Plasmodium falciparum Acta Pharmaceutica Sinica B Meplazumab CD147 Safety Tolerance Efficacy Nonclinical |
| title | Nonclinical safety, tolerance and pharmacodynamics evaluation for meplazumab treating chloroquine-resistant Plasmodium falciparum |
| title_full | Nonclinical safety, tolerance and pharmacodynamics evaluation for meplazumab treating chloroquine-resistant Plasmodium falciparum |
| title_fullStr | Nonclinical safety, tolerance and pharmacodynamics evaluation for meplazumab treating chloroquine-resistant Plasmodium falciparum |
| title_full_unstemmed | Nonclinical safety, tolerance and pharmacodynamics evaluation for meplazumab treating chloroquine-resistant Plasmodium falciparum |
| title_short | Nonclinical safety, tolerance and pharmacodynamics evaluation for meplazumab treating chloroquine-resistant Plasmodium falciparum |
| title_sort | nonclinical safety tolerance and pharmacodynamics evaluation for meplazumab treating chloroquine resistant plasmodium falciparum |
| topic | Meplazumab CD147 Safety Tolerance Efficacy Nonclinical |
| url | http://www.sciencedirect.com/science/article/pii/S2211383520306213 |
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