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A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors
- Source :
- Proceedings of the National Academy of Sciences. 104:4071-4076
- Publication Year :
- 2007
- Publisher :
- Proceedings of the National Academy of Sciences, 2007.
-
Abstract
- An array of cell-surface antigens expressed by human cancers have been identified as targets for antibody-based therapies. The great majority of these antibodies do not have specificity for cancer but recognize antigens expressed on a range of normal cell types (differentiation antigens). Over the past two decades, our group has analyzed thousands of mouse monoclonal antibodies for cancer specificity and identified a battery of antibodies with limited representation on normal human cells. The most tumor-specific of these antibodies is 806, an antibody that detects a unique epitope on the epidermal growth factor receptor (EGFR) that is exposed only on overexpressed, mutant, or ligand-activated forms of the receptor in cancer. In vitro immunohistochemical specificity analysis shows little or no detectable 806 reactivity with normal tissues, even those with high levels of wild-type (wt)EGFR expression. Preclinical studies have demonstrated that 806 specifically targets a subset of EGFR expressed on tumor cells, and has significant anti-tumor effects on human tumor xenografts, primarily through abrogation of signaling pathways. The present clinical study was designed to examine the in vivo specificity of a chimeric form of mAb 806 (ch806) in a tumor targeting/biodistribution/pharmacokinetic analysis in patients with diverse tumor types. ch806 showed excellent targeting of tumor sites in all patients, no evidence of normal tissue uptake, and no significant toxicity. These in vitro and in vivo characteristics of ch806 distinguish it from all other antibodies targeting EGFR.
- Subjects :
- Male
medicine.drug_class
Antineoplastic Agents
Monoclonal antibody
Epitope
Antigen
Epidermal growth factor
Cell Line, Tumor
Neoplasms
medicine
Humans
Epidermal growth factor receptor
Aged
Multidisciplinary
biology
Cell Membrane
Indium Radioisotopes
Antibodies, Monoclonal
Middle Aged
Biological Sciences
Molecular biology
ErbB Receptors
Monoclonal
biology.protein
Immunohistochemistry
Female
Immunotherapy
Antibody
Neoplasm Transplantation
Signal Transduction
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 104
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....f3e28e712a4f814ec60667b9de4160ed
- Full Text :
- https://doi.org/10.1073/pnas.0611693104