ArticleMolecular cancer2012
Tumor penetration and epidermal growth factor receptor saturation by panitumumab correlate with antitumor activity in a preclinical model of human cancer.
Article in Molecular cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- A cross-reactive pH-dependent EGFR antibody with improved tumor selectivity and penetration obtained by structure-guided engineering.Molecular therapy oncolytics · 2022Article
- Integration of liquid biopsy and pharmacogenomics for precision therapy of EGFR mutant and resistant lung cancers.Molecular cancer · 2022Review
- KEuropean biophysics journal : EBJ · 2021Article
- Which factors matter the most? Revisiting and dissecting antibody therapeutic doses.Drug discovery today · 2021Review
- Predicting Therapeutic Antibody Delivery into Human Head and Neck Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- A Bioluminescence Resonance Energy Transfer-Based Approach for Determining Antibody-Receptor Occupancy In Vivo.iScience · 2019Article
- A Novel Anti-EGFR mAb Ame55 with Lower Toxicity and Better Efficacy than Cetuximab When Combined with Irinotecan.Journal of immunology research · 2019Article
- Exploration of a F(ab')Cancer biotherapy & radiopharmaceuticals · 2018Article
- Small-Format Drug Conjugates: A Viable Alternative to ADCs for Solid Tumours?Antibodies (Basel, Switzerland) · 2018Review
- Receptor occupancy assessment by flow cytometry as a pharmacodynamic biomarker in biopharmaceutical development.Cytometry. Part B, Clinical cytometry · 2016Review
- Antigen specificity can be irrelevant to immunocytokine efficacy and biodistribution.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- EGFR ligands as pharmacodynamic biomarkers in metastatic colorectal cancer patients treated with cetuximab and irinotecan.Targeted oncology · 2014Article
- Mechanistic considerations for the use of monoclonal antibodies for cancer therapy.Cancer biology & medicine · 2014Review
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10 authors.
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Abstract
backgroundSuccessful treatment of solid tumors relies on the ability of drugs to penetrate into the tumor tissue.
methodsWe examined the correlation of panitumumab (an anti-epidermal growth factor [EGFR] antibody) tumor penetration and EGFR saturation, a potential obstacle in large molecule drug delivery, using pharmacokinetics, pharmacodynamics, and tumor growth rate in an A431 epidermoid carcinoma xenograft model of human cancer. To determine receptor saturation, receptor occupancy, and levels of proliferation markers, immunohistochemical and flow cytometric methods were used. Pharmacokinetic data and modeling were used to calculate growth characteristics of panitumumab-treated tumors.
resultsTreatment with panitumumab in vivo inhibited pEGFR, Ki67 and pMAPK levels vs control. Tumor penetration and receptor saturation were dose- and time-dependent, reaching 100% and 78%, respectively. Significant tumor inhibition and eradication (p < 0.05) were observed; plasma concentration associated with tumor eradication was estimated to be 0.2 μg/ml. The tumor inhibition model was able to describe the mean tumor growth and death rates.
conclusionsThese data demonstrate that the antitumor activity of panitumumab correlates with its ability to penetrate into tumor tissue, occupy and inhibit activation of EGFR, and inhibit markers of proliferation and MAPK signaling.
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