Patritumab

Patritumab (Human Anti-ERBB3 Recombinant Antibody) is a neutralizing monoclonal antibody to ERBB3. Patritumab shows a synergy with Cetuximab (HY-P9905), potently inhibits the phosphorylation of EGFR, HER2, HER3, ERK, and Akt. Patritumab also induces cell apoptosis and suppresses the growth of pancreatic, non-small cell lung cancer, and colorectal cancer xenograft tumors[1].

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Signaling Pathways >> Epigenetics >> PARP

Signaling Pathways >> Apoptosis >> Survivin

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

Signaling Pathways >> PI3K/Akt/mTOR >> Akt

Signaling Pathways >> MAPK/ERK Pathway >> ERK

Signaling Pathways >> Cell Cycle/DNA Damage >> PARP

Signaling Pathways >> Stem Cell/Wnt >> ERK

Patritumab targets to the extracellular domain (ECD) of HER3 and (10 μg/mL; 5 d) induces DiFi-HRG4 cells apoptosis[1]. Patritumab (10 μg/mL; 6 h) markedly inhibits the phosphorylation of HER3 and AKT, without affecting that of ERK, in DiFi-HRG4 cells[1]. Patritumab (10 μg/mL; 48 h) also induces the cleavage of PARP accompanied with both up-regulation of BIM and down-regulation of survivin expression[1]. Western Blot Analysis[1] Cell Line: DiFi-HRG cells Concentration: 10 μg/mL Incubation Time: 6 hours Result: Inhibited the phosphorylation of HER3 and AKT as well as down-regulated survivin expression.

Patritumab (1 mg/mouse; i.p.; twice a week for 4 weeks) combines with 1 mg Cetuximab and restores Cetuximab sensitivity in DiFi-HRG tumor xenografts model in mice[1]. Heregulin produced by colorectal cancer tumors harboring wild-type KRAS induces Cetuximab resistance, and that combination therapy with cetuximab and patritumab overcomes such resistance in vivo[1]. Animal Model: Female athymic nude mice (BALB/c; 5-6 weeks old) with DiFi-Mock1 or DiFi-HRG4 (s.c.)[1] Dosage: 1 mg/body Administration: Intraperitoneal injection; twice a week for 4 weeks Result: Individual Patritumab treatment had little effect on the growth of tumors formed by either cell line. Combination of Cetuximab and Patritumab induced substantial regression of DiFi-HRG4 xenografts.

[1]. Kawakami H, et al. The anti-HER3 antibody patritumab abrogates cetuximab resistance mediated by heregulin in colorectal cancer cells. Oncotarget. 2014 Dec 15;5(23):11847-56.