A Native Human Monoclonal Antibody Targeting HCMV gB (AD-2 Site I)
Autor: | Lawrence M. Kauvar, Edgar Tenorio, Michael M McVoy |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Hyperimmune globulin Human cytomegalovirus medicine.drug_class Cytomegalovirus Review Monoclonal antibody Catalysis Virus Epitope lcsh:Chemistry Inorganic Chemistry 03 medical and health sciences Viral Envelope Proteins medicine Humans Physical and Theoretical Chemistry Progenitor cell lcsh:QH301-705.5 Molecular Biology Spectroscopy Tropism biology cell tropism Organic Chemistry Antibodies Monoclonal congenital transmission General Medicine neutralization medicine.disease Virology Antibodies Neutralizing 3. Good health Computer Science Applications conserved site 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 monoclonal antibody biology.protein immune suppression Ex vivo |
Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 19, Iss 12, p 3982 (2018) |
ISSN: | 1422-0067 |
Popis: | Hyperimmune globulin (HIG) has shown efficacy against human cytomegalovirus (HCMV) for both transplant and congenital transmission indications. Replicating that activity with a monoclonal antibody (mAb) offers the potential for improved consistency in manufacturing, lower infusion volume, and improved pharmacokinetics, as well as reduced risk of off-target reactivity leading to toxicity. HCMV pathology is linked to its broad cell tropism. The glycoprotein B (gB) envelope protein is important for infections in all cell types. Within gB, the antigenic determinant (AD)-2 Site I is qualitatively more highly-conserved than any other region of the virus. TRL345, a high affinity (Kd = 50 pM) native human mAb to this site, has shown efficacy in neutralizing the infection of fibroblasts, endothelial and epithelial cells, as well as specialized placental cells including trophoblast progenitor cells. It has also been shown to block the infection of placental fragments grown ex vivo, and to reduce syncytial spread in fibroblasts in vitro. Manufacturing and toxicology preparation for filing an IND (investigational new drug) application with the US Food and Drug Administration (FDA) are expected to be completed in mid-2019. |
Databáze: | OpenAIRE |
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