Pharmacokinetics and Biodistribution Study of 7A7 Anti-Mouse Epidermal Growth Factor Receptor Monoclonal Antibody and Its Fragment in an Immunocompetent Mouse Model

Abstract

Immunocompetent mice, Fc receptor γ-chain deficient mice (Fcer1g−/−), and molecular tools as F(ab′)2 bivalent fragments appear as the most suitable biological models to study the mechanisms of the action of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs). In vivo experiments contrasting antitumor effects of whole Abs and their bivalent fragments commonly involve a previous comparative pharmacokinetics study. In this paper, pharmacokinetics and biodistribution of an anti-mouse EGFR Ab were assessed using immunocompetent mice. 125I-labeled 7A7 mAb holds an elimination half-life (t1/2β) of 23.1 h in C57BL/6 mice. Accumulation of mAb was found in liver, spleen, kidneys, and mostly in lungs. We used an ELISA method to determine the t1/2β of a 7A7 mAb using the same experimental setting. Results from this new analysis revealed a t1/2β of 23.9 h, supporting this method as a safer and easier system to evaluate pharmacokinetics parameters of mAbs targeting mouse EGFR. Using this system we also studied pharmacokinetics of 7A7 F(ab′)2 fragment. A tenfold difference between the mAb and fragment t1/2β was found. These data support the use of the 7A7 F(ab′)2 fragment in in vivo studies to explore the contribution of the EGFR signaling blockade and the Fc region to the antitumor effect of 7A7 mAb in this autologous scenario.

177Lu radiolabeling and preclinical theranostic study of 1C1m-Fc: an anti-TEM-1 scFv-Fc fusion protein in soft tissue sarcoma

“…This experiment revealed specific tumor targeting in the two mouse xenograft models with no impact of the Kiovig™ co-injection on biodistribution. The [177Lu]Lu-1C1m-Fc was found to enrich mainly in the liver and the spleen, as has been observed for many antibodies [ 28 , 30 , 31 ]. Quantitative PCR, performed by other groups on biopsies taken from mice upon sacrifice has shown an absence of detectable TEM-1 in the liver, confirming this uptake to be non-specific in nature.…”

Characterization of 7A7, an anti-mouse EGFR monoclonal antibody proposed to be the mouse equivalent of cetuximab

“…However, the same was true for HPV38 tumours, which we were able to confirm express EGFR by multiple methods. In conclusion, contrary to the findings of previously published studies [ 13 , 14 , 22 , 25 – 27 ], our results did not find any evidence to support that 7A7 is able to recognise mouse or human EGFR on either cell lines or tumour tissue.…”

Immuno-PET Imaging and Pharmacokinetics of an Anti-CEA scFv-based Trimerbody and Its Monomeric Counterpart in Human Gastric Carcinoma-Bearing Mice

“…Values obtained for the trimerbody are quite similar to those previously reported in the literature for F­(ab′) 2 fragments, which have similar molecular weight (100 kDa). For example, T 1/2β and clearance values of 2.25 ± 0.02 h and 0.300 ± 0.007 mL/h were found in mice for a F­(ab′) 2 fragment of 7A7 mAb after intravenous administration in wild type mice . Similar blood clearance properties were also reported for the F­(ab′) 2 fragments of IgG1…”