Non-fucosylated Anti-Human EGFR Therapeutic Antibody, an ADCC-Enhanced Biobetter [Lot: CB20-PZ05] (CAT#: BioBet-005ZP) Datasheet

Target
EGFR
Isotype
Human Antibody
Description
ADCC-enhanced Panitumumab is a non-fucosylated anti-EGFR therapeutic biobetter antibody. Creative Biolabs' Afuco™ technology platform allows for the control of glycosylation level, thereby achieving ADCC-Enhanced Anti-EGFR Panitumumab, a biobetter by reducing fucosylation of the Fc region of Panitumumab, leading to an increased binding affinity for the FcyR receptor on immune effector cells.
More specifically, the afucosylated therapeutic biobetter antibody was generated by recombinant DNA technology. It has been produced in CHO cells that are deficient for fucosylation and purified by affinity chromatography with protein G. The absence of the fucose residue from the N-glycans of IgG-Fc results in dramatic enhancement of antibody-dependent cellular cytotoxicity (ADCC).
Indication
Metastatic Colorectal Cancer (MCRC)
Metastatic Squamous Cell Carcinoma of the Head and Neck
Advanced squamous cell carcinoma of the head and neck
Classification
Therapeutic antibody; biobetter
Patent
Not Available
Status
Preclinical

Cooperation Seeking

Creative Biolabs is interested in collaborating with potential partners (include but not limit to major pharma or biotech firms) to further co-develop ADCC-enhanced Panitumumab. For commercial partners interested in our ADCC-enhanced therapeutic antibodies, Creative Biolabs welcomes collaboration. Here are two ways for your choice, and please contact us for more details.
1) Collaborate with us and co-develop the programs from discovery phase to IND enabling. Costs will be shared.
2) Become a licensed candidate of our programs.
Looking forward to cooperating with you in the near future.
Official Name
EGFR
Full Name
epidermal growth factor receptor
Background
The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer.
Alternative Names
EGFR; epidermal growth factor receptor; ERBB; HER1; mENA; ERBB1; PIG61; NISBD2; proto-oncogene c-ErbB-1; cell growth inhibiting protein 40; erb-b2 receptor tyrosine kinase 1; cell proliferation-inducing protein 61; receptor tyrosine-protein kinase erbB-1; avian erythroblastic leukemia viral (v-erb-b) oncogene homolog
Gene ID
UniProt ID
Cellular Localization
Plasma membrane, Extracellular region or secreted Cytosol, Endosome, Nucleus, Golgi apparatus, ER.
HGNC
OMIM
Involvement in Disease
Diseases associated with EGFR include Inflammatory Skin And Bowel Disease, Neonatal, 2 and Lung Cancer.
Related Pathways
Its related pathways are DAG and IP3 signaling and Association Between Physico-Chemical Features and Toxicity Associated Pathways.
Function
1.Receptor tyrosine kinases bind to EGF family ligands and activate several signal cascades to transduce extracellular signals into appropriate cellular responses (PubMed: 2790960, PubMed: 10805725, PubMed: 27153536). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG, and HBEGF/heparin binding EGF (PubMed: 2790960, PubMed: 7679104, PubMed: 8144591, PubMed: 9419975, PubMed :15611079, PubMed:12297049, PubMed:27153536, PubMed:20837704). Ligand binding triggers homo- and/or heterodimerization of the receptor and autophosphorylation of key cytoplasmic residues. Phosphorylated receptors absorb adaptor proteins like GRB2, which in turn activate complex downstream signaling cascades. Activate at least 4 major downstream signal cascades, including RAS-RAF-MEK-ERK, PI3 kinase-akt, PLCgamma-PKC and STATs modules (PubMed: 27153536). It is also possible to activate the nf-kpa-b signal cascade (PubMed: 11116146). It can also directly phosphorylate other proteins such as RGS16 to activate its GTPase activity, and possibly couple EGF receptor signals with G protein-coupled receptor signals (PubMed: 11602604). It also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/ -catenin (PubMed: 11483589). Through the interaction with CCDC88A/GIV, it positively regulates cell migration, retains EGFR on the cell membrane after ligand stimulation, promotes EGFR signaling, and triggers cell migration (PubMed:20462955). Play a role in improving learning and memory performance (through similarity). 2. Isoform 2 can act as an antagonist of EGF. 3. (Microbial infection) It acts as a receptor for hepatitis C virus (HCV) in liver cells and promotes its entry into cells. HCV entry is mediated by promoting the formation of the CD81-CLDN1 receptor complex which is essential for HCV entry and enhancing the membrane fusion of cells expressing HCV envelope glycoprotein.
Field of research
Cancer antibody; Signaling Transduction antibody
Post-translational modifications
Phosphorylation at Ser-695 is partial and occurs only if Thr-693 is phosphorylated. Phosphorylation at Thr-678 and Thr-693 by PRKD1 inhibits EGF-induced MAPK8/JNK1 activation. Dephosphorylation by PTPRJ prevents endocytosis and stabilizes the receptor at the plasma membrane. Autophosphorylation at Tyr-1197 is stimulated by methylation at Arg-1199 and enhances interaction with PTPN6. Autophosphorylation at Tyr-1092 and/or Tyr-1110 recruits STAT3. Dephosphorylated by PTPN1 and PTPN2. Monoubiquitinated and polyubiquitinated upon EGF stimulation; which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting. Polyubiquitin linkage is mainly through 'Lys-63', but linkage through 'Lys-48', 'Lys-11' and 'Lys-29' also occurs. Deubiquitination by OTUD7B prevents degradation. Ubiquitinated by RNF115 and RNF126 (By similarity). Methylated. Methylation at Arg-1199 by PRMT5 stimulates phosphorylation at Tyr-1197.
Trade name
Erbitux
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Accession Number
DB01269
CAS number
339177-26-3
Antibody Isotype
Human Antibody
Antibody Clone
Panitumumab
Description
Panitumumab (ABX-EGF) is a recombinant fully human monoclonal antibody that specifically binds human epidermal growth factor receptor (EGFR). Panitumumab is manufactured by Amgen and is an antitumor drug.
Indication
Metastatic Colorectal Cancer (MCRC)
Metastatic Squamous Cell Carcinoma of the Head and Neck
Advanced squamous cell carcinoma of the head and neck
Synonyms
ABX-EGF
UNII
6A901E312A

Panitumumab binds to epidermal growth factor receptor (EGFr) on both normal and tumor cells and is widely used to treat metastatic CRC. EGFr is overexpressed in many colorectal cancers. Panitumumab competitively inhibits the binding of epidermal growth factor (EGF) and TGFα, thereby reducing their effect on cell growth and metastasis. Mouse model experiments show that Panitumumab can target tumor cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and increase antitumor activity.

Panitumumab is used in combination with irinotecan, and is suitable for the treatment of metastatic colorectal cancer expressing EGFR in patients who are difficult to treat with irinotecan-based chemotherapy. Panitumumab monotherapy can be used to treat metastatic colorectal cancer expressing EGFR in patients who are intolerant to irinotecan-based chemotherapy.

All products and services are for Research Use Only. Do Not use in humans.

ONLINE INQUIRY

Creative Biolabs has established a team of customer support scientists ready to discuss ADCC/CDC optimization strategies, antibody production, bioinformatics analysis and other molecular biology/biotechnology issues.

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