Peptide mimotopes recognized by antibodies cetuximab and matuzumab induce a functionally equivalent anti-EGFR immune response

Hartmann, C; Müller, Nina; Blaukat, Andree; Koch, Joachim; Benhar, Itai; Wels, Winfried S.

doi:10.1038/onc.2010.195

Cited by 33 publications

(31 citation statements)

References 29 publications

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“…We therefore concluded that the epitopes targeted by panitumumab and cetuximab are not identical. In fact, this lack of cross-reactivity was expected as entirely unrelated peptides had previously been described to structurally mimic the cetuximab epitope [33,34]. However, these data do not exclude a substantial overlap of both epitopes.…”

Section: The Epitope-mimicking Phage Selected On Panitumumab Are Not mentioning

confidence: 60%

Functional Dissection of the Epidermal Growth Factor Receptor Epitopes Targeted by Panitumumab and Cetuximab

et al. 2012

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Cetuximab and panitumumab, two antibodies targeting the extracellular domain of the epidermal growth factor receptor (EGFR), are of major clinical importance particularly in the treatment of metastatic colorectal cancer. As patients may acquire resistance-mediating mutations within the extracellular EGFR domain, functional dissection of the exact binding sites of EGFR targeting antibodies may help predict treatment responses. We therefore assessed the epitope recognition of panitumumab by screening phage-displayed random cyclic 7mer and linear 12mer peptide libraries on this antibody. Phage screenings revealed two strong, potentially epitope-mimicking consensus motifs targeted by panitumumab. A computational approach was used to map the sequences back to the potential epitope region on domain III of EGFR. The presumed epitope regions (386)WPEXRT(391) and a biochemically similar though discontinuous region P349-F352-D355 on a neighboring loop of domain III could be confirmed as part of the functionally relevant binding site of panitumumab by site-directed mutational analysis. To more accurately differentiate the panitumumab epitope from the previously characterized cetuximab epitope, binding studies were performed on a broad range of additional mutants. Taken together, this analysis revealed two large, partially overlapping functional epitopes consisting of 17 critical amino acid positions. Four of these positions were selectively targeted by cetuximab (I467, S468, Q408, and H409), whereas another four were selectively recognized by panitumumab (W386, E388, R390, and T391). In view of the clinical significance of extracellular domain mutations, our data may help guide treatment decisions in selected patients receiving EGFR-targeted therapies.

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Section: The Epitope-mimicking Phage Selected On Panitumumab Are Not mentioning

confidence: 60%

Functional Dissection of the Epidermal Growth Factor Receptor Epitopes Targeted by Panitumumab and Cetuximab

et al. 2012

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“…The selection system might be further refined by the availability of a peptide capable of competing off Erbitux bound to huEGFRt. 28 This would be advantageous when selection is timed close to patient infusion where residual cell bound Erbitux could elicit human anti-chimeric antibody responses that would limit the survival of subsequent cell doses.…”

Section: Discussionmentioning

confidence: 99%

A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells

Wang

Chang

Wong

et al. 2011

Blood

518

507

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“…While some peptides selected on cetuximab resemble the array of side chains forming its epitope, 36 other immunological mimics do not show an obvious similarity to EGFR. 37 Some attempts to find the correspondence between selected peptides and Ag sequences have resulted in the identification of antigenic regions totally different from the actual epitope(s).…”

Section: Discussionmentioning

confidence: 99%

Delineating the functional map of the interaction between nimotuzumab and the epidermal growth factor receptor

Tundidor

García-Hernández

Pupo

et al. 2014

mAbs

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Peptide mimotopes recognized by antibodies cetuximab and matuzumab induce a functionally equivalent anti-EGFR immune response

Cited by 33 publications

References 29 publications

Functional Dissection of the Epidermal Growth Factor Receptor Epitopes Targeted by Panitumumab and Cetuximab

Functional Dissection of the Epidermal Growth Factor Receptor Epitopes Targeted by Panitumumab and Cetuximab

A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells

Delineating the functional map of the interaction between nimotuzumab and the epidermal growth factor receptor

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