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#monoclonal antibody therapy

2 public questions tagged with this topic.

Immunological Applications

Trastuzumab (Herceptin) is used in treatment of:

HER2 proto-oncogene ERBB2 located chromosome 17q12 encoding 185 kDa receptor tyrosine kinase member EGFR family characterized by extracellular cysteine-rich domains, single transmembrane helix, and intracellular kinase domain. Amplification in 15 to 20 percent invasive breast carcinomas leads to overexpression up to two million receptors per cell versus normal 20,000, facilitating ligand independent homodimerization and heterodimerization with HER3 bound to neuregulin, triggering transphosphorylation of tyrosine residues creating docking sites for Shc, Grb2, p85 subunit of PI3K. Downstream PI3

Ref: Slamon et al NEJM 2001 344:783 HER2 trastuzumab domain IV; Harari & Yarden Oncogene 2000 HER2 dimer PI3K signaling.

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Immunological Applications

Which of the following is an example of therapeutic monoclonal antibody?

Rituximab illustrates first FDA approved chimeric therapeutic monoclonal antibody transforming oncology and autoimmunity management. Engineering used recombinant DNA swapping murine variable regions conferring CD20 specificity onto human IgG1 kappa constant domains, approximately 65 percent human to reduce HAMA human anti-mouse antibody response while retaining effector function. Constant region Fc glycosylated at Asn297 in CH2 domain with fucosylated biantennary glycan necessary for high affinity interaction with FcγRIIIa on natural killer cells and macrophages. Production in Chinese hamster

Ref: FDA Monoclonal antibody Rituximab label; Nature Rev Drug Discov 2018 17:31 chimeric anti-CD20 B depletion lymphoma.

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