Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy

Yang, Xiaodong; Jia, Xiao‐Chi; Corvalan, J. R. F.; Wang, Ping; Davis, Clay

doi:10.1016/s1040-8428(00)00134-7

Cited by 430 publications

(242 citation statements)

References 16 publications

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“…While several EGFR therapeutics exist for blocking ligand binding and subsequent dimerization, previous studies have focused on monitoring receptor activation as a measure of therapeutic efficacy (25,26). A better measure of efficacy would be to directly examine the dimerization event that these antibodies were designed to impair.…”

Section: Therapeutic Anti-egfr Monoclonals Have Differential Effects mentioning

confidence: 99%

In Situ Analysis of Mutant EGFRs Prevalent in Glioblastoma Multiforme Reveals Aberrant Dimerization, Activation, and Differential Response to Anti-EGFR Targeted Therapy

Gajadhar

Bogdanovic

Muñoz

et al. 2012

Molecular Cancer Research

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Aberrations in epidermal growth factor receptor (EGFR/ErbB1) are the most common oncogenic alterations in glioblastoma multiforme (GBM), the most common primary brain tumor. Interactions between wild-type (wt) and mutant EGFRs and their subsequent activation are of biologic and potential therapeutic importance in GBMs. We recently showed that in situ proximity ligation assay (PLA) allows for quantitative evaluation of EGFR dimerization and activation in intact cells. Using this in situ platform, we show the aberrant homo-/heterodimeric properties of EGFRvIII and EGFRc958 mutants, the two most common EGFR mutants in GBMs. In addition, dimer phosphoactivation status could be detected by PLA with superior signal-noise ratio (>17-fold) and sensitivity (>16-fold) than immunofluorescence-based phospho-EGFR measurements. Dimer activation analysis indicated quantitative activation differences of mutant dimers. These aberrant features were not overexpression dependent but appeared independent of cellular expression levels, suggesting inherent properties of the mutant receptors. Moreover, we observed in situ detection of EGFRwt-EGFRvIII heterodimerization in GBM specimens, supporting our cell line observations. Notably, currently used anti-EGFR therapeutics, such as cetuximab, matuzumab, and panitumumab, could effectively block EGFRwt dimerization and activation but did not equally impair EGFRvIII homodimers, EGFRwt-EGFRvIII, or EGFRvIII-EGFRc958 heterodimers. EGFRvIII appears to have intrinsic phosphoactivation independent of dimerization as matuzumab blockade of homodimerization had no effect on receptor phosphorylation levels. These data suggest differences in the dimerization-blocking efficacy of EGFR monoclonal antibodies as mutant EGFR dimer configurations prevalent in GBMs can evade blockade by anti-EGFR treatments. Further studies are warranted to evaluate whether this evasion contributes to poor therapeutic response or resistance. Mol Cancer Res; 10(3); 428-40. Ó2012 AACR.

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Section: Therapeutic Anti-egfr Monoclonals Have Differential Effects mentioning

confidence: 99%

In Situ Analysis of Mutant EGFRs Prevalent in Glioblastoma Multiforme Reveals Aberrant Dimerization, Activation, and Differential Response to Anti-EGFR Targeted Therapy

Gajadhar

Bogdanovic

Muñoz

et al. 2012

Molecular Cancer Research

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“…phorylation. However, unlike cetuximab, panitumumab does not induce receptor degradation upon internalization, suggesting that EGFR may be recycled to the cell surface [34]. Pharmacokinetic data have shown that serum panitumumab concentrations, when given as an i.v.…”

Section: Panitumumab (Abx-egf)mentioning

confidence: 99%

Cetuximab and Other Anti–Epidermal Growth Factor Receptor Monoclonal Antibodies in the Treatment of Non-Small Cell Lung Cancer

et al. 2009

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“…ABX-EGF blocks receptor binding to EGF and transforming growth factor-a, inhibits EGFR tyrosine phosphorylation and tumor cell activation. ABX-EGF prevents tumor formation and eradicates large, established A431 tumors in xenograft models (Yang et al, 2001;Foon et al, 2004). A phase I clinical trial has demonstrated antitumor activity in several tumor types, and the results from a phase II trial for renal cell cancer also showed modest activity (Rowinsky et al, 2004).…”

Section: Naked Antibodiesmentioning

confidence: 99%

Novel antibodies as anticancer agents

2007

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In recent years antibodies, whether generated by traditional hybridoma technology or by recombinant DNA strategies, have evolved from Paul Ehrlich's 'magic bullets' to a modern age 'guided missile'. In the recent years of immunologic research, we are witnessing development in the fields of antigen screening and protein engineering in order to create specific anticancer remedies. The developments in the field of recombinant DNA, protein engineering and cancer biology have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, and regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals: monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and a high-affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. This review will screen some of the many novel antibodies and antibody-based approaches that are being currently developed for clinical applications as the new generation of anticancer agents.

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Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy

Cited by 430 publications

References 16 publications

In Situ Analysis of Mutant EGFRs Prevalent in Glioblastoma Multiforme Reveals Aberrant Dimerization, Activation, and Differential Response to Anti-EGFR Targeted Therapy

In Situ Analysis of Mutant EGFRs Prevalent in Glioblastoma Multiforme Reveals Aberrant Dimerization, Activation, and Differential Response to Anti-EGFR Targeted Therapy

Cetuximab and Other Anti–Epidermal Growth Factor Receptor Monoclonal Antibodies in the Treatment of Non-Small Cell Lung Cancer

Novel antibodies as anticancer agents

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