Pharmacological and immunological characteristics of the therapeutic anti-EGFR antibodies cetuximab, panitumumab, and nimotuzumab.

Stroh, Christopher; Reusch, Christof; Schmidt, Jörg; Splittgerber, Jörg; Wesolowski, John S.; Blaukat, Andree

doi:10.1200/jco.2010.28.15_suppl.e13025

Cited by 3 publications

(6 citation statements)

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“…The EC50 value for cetuximab on A431 cells was calculated to be 0.07 n m being in the range of the published affinity constants between 0.1 and 5.2 n m indicating the reliability of the experiment. [ 29–31 ] A6 and A12 showed the highest affinities toward A431‐bound EGFR with EC50 values of 0.08 and 0.34 n m , respectively, while A2 (11.50 n m ) and A5 (6.0 n m ) showed lower EC50 values. Furthermore, we performed affinity titration experiments utilizing flow cytometry (Figure S8, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

“…Obtained EC50 values ranged between 27.2 for A6 and 59.5 n m for A2, while cetuximab exhibited 8.9 n m , which resembles prior reported affinities. [ 30,31 ]…”

Section: Resultsmentioning

confidence: 99%

“…Nevertheless, the obtained EC50 values of the cetuximab control (0.07 and 8.9 n m ) closely resembles prior published affinities in the range of 0.1 and 5.2 n m , determined by different methods. [ 29–31 ]…”

Section: Discussionmentioning

confidence: 99%

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Isolation of Common Light Chain Antibodies from Immunized Chickens Using Yeast Biopanning and Fluorescence‐Activated Cell Sorting

Bogen

Storka

Yanakieva

et al. 2020

Biotechnology Journal

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The phylogenetic distance between chickens and humans accounts for a strong immune response and a broader epitope coverage compared to rodent immunization approaches. Here the authors report the isolation of common light chain (cLC)‐based chicken monoclonal antibodies from an anti‐epidermal growth factor receptor (EGFR) immune library utilizing yeast surface display in combination with yeast biopanning and fluorescence‐activated cell sorting (FACS). For the selection of high‐affinity antibodies, a yeast cell library presenting cLC‐comprising fragment antigen binding (Fab) fragments is panned against hEGFR‐overexpressing A431 cells. The resulting cell–cell‐complexes are sorted by FACS resulting in gradual enrichment of EGFR‐binding Fabs in three sorting rounds. The isolated antibodies share the same light chain and show high specificity for EGFR, resulting in selective binding to A431 cells with notable EC50 values. All identified antibodies show very good aggregation propensity profiles and thermostabilities. Additionally, epitope binning demonstrates that these cLC antibodies cover a broad epitope space. Isolation of antibodies from immunized chickens by yeast cell biopanning makes an addition to the repertoire of methods for antibody library screening, paving the way for the generation of cLC‐based bispecific antibodies against native mammalian receptors.

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Section: Resultsmentioning

confidence: 99%

“…Obtained EC50 values ranged between 27.2 for A6 and 59.5 n m for A2, while cetuximab exhibited 8.9 n m , which resembles prior reported affinities. [ 30,31 ]…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Isolation of Common Light Chain Antibodies from Immunized Chickens Using Yeast Biopanning and Fluorescence‐Activated Cell Sorting

Bogen

Storka

Yanakieva

et al. 2020

Biotechnology Journal

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“…The nanomolar K D values derived from SPR spectroscopy and flow cytometry experiments were in some cases nearly the same and in other cases either higher or lower, but only in the case of one scFv clone was the difference in the values greater than 5-fold . Similarly, for cetuximab and panitumumab affinity constants measured by flow cytometry and SPR spectroscopy were compared, the former yielded K D values of 5 nM for cetuximab and 4 nM for panitumumab in binding to A431 cells, which were also higher values than those determined by SPR spectroscopy …”

Section: Resultsmentioning

confidence: 76%

SNAP-Tag Technology: A Useful Tool To Determine Affinity Constants and Other Functional Parameters of Novel Antibody Fragments

et al. 2016

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Antibody derivatives, such as the single chain fragment variable (scFv), can be developed as diagnostic and therapeutic tools in cancer research, especially in the form of fusion proteins. Such derivatives are easier to produce and modify than monoclonal antibodies (mAbs) and achieve better tissue/tumor penetration. The genetic modification of scFvs is also much more straightforward than the challenging chemical modification of mAbs. Therefore, we constructed two scFvs derived from the approved monoclonal antibodies cetuximab (scFv2112) and panitumumab (scFv1711), both of which are specific for the epidermal growth factor receptor (EGFR), a well-characterized solid tumor antigen. Both scFvs were genetically fused to the SNAP-tag, an engineered version of the human DNA repair enzyme O(6)-alkylguanine DNA alkyltransferase that allows the covalent coupling of benzylguanine (BG)-modified substrates such as fluorescent dyes. The SNAP-tag achieves controllable and irreversible protein modification and is an important tool for experimental studies in vitro and in vivo. The affinity constant of a scFv is a key functional parameter, especially in the context of a fusion protein. Therefore, we developed a method to define the affinity constants of scFv-SNAP fusion proteins by surface plasmon resonance (SPR) spectroscopy. We could confirm that both scFvs retained their functionality after fusion to the SNAP-tag in a variety of procedures and assays, including ELISA, flow cytometry, and confocal microscopy. The experimental procedures described herein, and the new protocol for affinity determination by SPR spectroscopy, are suitable for the preclinical evaluation of diverse antibody formats and derivatives.

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“…[1][2][3] The ability of cetuximab to stimulate marked, dose-dependent ADCC activity contrasts with that of other anti-EGFR antibodies, such as panitumumab and nimotuzumab, which display little or no activity in this regard. [4] The development of human anti-chimeric antibodies is a class effect of chimeric mAbs. [5] Non-neutralizing anti-cetuximab antibodies that had no apparent effect on the antitumor activity or tolerability of the drug were detected in 49 (5%) of 1001 patients studied.…”

Section: Pharmacologic Propertiesmentioning

confidence: 99%

Spotlight on Cetuximab in Squamous Cell Carcinoma of the Head and Neck†

Frampton

2011

BioDrugs

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Cetuximab (Erbitux®) is a chimeric monoclonal antibody directed against the human epidermal growth factor receptor (EGFR). EGFR is overexpressed and/or upregulated in most squamous cell carcinomas of the head and neck (SCCHN); this overexpression is associated with more aggressive disease and poorer prognosis. In the EU, cetuximab is approved in combination with radiation therapy for the treatment of locally advanced SCCHN and in combination with platinum-based chemotherapy for the treatment of recurrent and/or metastatic SCCHN. In randomized, open-label, multinational, phase III clinical trials, cetuximab plus radiotherapy significantly improved the duration of locoregional control (primary endpoint) compared with radiotherapy alone in patients with locally advanced SCCHN, while cetuximab plus first-line platinum-based chemotherapy significantly improved overall survival (primary endpoint) compared with first-line platinum-based chemotherapy alone in patients with recurrent and/or metastatic SCCHN. The efficacy benefits of cetuximab-based combination therapy were achieved without an adverse impact on patients' health-related quality of life. In addition, cetuximab had an acceptable tolerability profile when added to radiotherapy or platinum-based chemotherapy; in particular, it did not exacerbate the toxicities commonly associated with these other treatment modalities. Cetuximab-related adverse events, which include skin rash, hypomagnesemia and infusion-related reactions, are mostly mild to moderate in severity and manageable. Thus, cetuximab-based combination therapy is a valuable treatment option in patients with SCCHN. In the setting of locally advanced, unresectable disease, cetuximab plus radiotherapy offers an alternative approach to the current standard of care, namely platinum-based chemotherapy plus radiotherapy (chemoradiotherapy). Based on informal comparisons, cetuximab plus radiotherapy appears to be at least as effective as chemoradiotherapy and, moreover, less toxic; however, formal comparisons of these regimens are required before their relative efficacy and tolerability can be conclusively determined. In the setting of recurrent and/or metastatic SCCHN, cetuximab plus platinum-based chemotherapy provides a first-line treatment of choice for fit patients in whom palliative chemotherapy is indicated.

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Pharmacological and immunological characteristics of the therapeutic anti-EGFR antibodies cetuximab, panitumumab, and nimotuzumab.

Cited by 3 publications

References 0 publications

Isolation of Common Light Chain Antibodies from Immunized Chickens Using Yeast Biopanning and Fluorescence‐Activated Cell Sorting

Isolation of Common Light Chain Antibodies from Immunized Chickens Using Yeast Biopanning and Fluorescence‐Activated Cell Sorting

SNAP-Tag Technology: A Useful Tool To Determine Affinity Constants and Other Functional Parameters of Novel Antibody Fragments

Spotlight on Cetuximab in Squamous Cell Carcinoma of the Head and Neck†

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