Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody

Foon, Kenneth A.; Yang, Xiao; Weiner, Louis M.; Belldegrun, Arie S.; Figlin, Robert A.; Crawford, Jeffrey; Rowinsky, Eric K.; Dutcher, Janice P.; Vogelzang, Nicholas J.; Gollub, Jared; Thompson, John A.; Schwartz, Garry; Bukowski, Ronald M.; Roskos, Lorin; Schwab, Gisela

doi:10.1016/j.ijrobp.2003.09.098

Cited by 207 publications

(112 citation statements)

References 28 publications

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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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Section: Naked Antibodiesmentioning

confidence: 99%

Novel antibodies as anticancer agents

2007

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“…Many of the antibodies in development or currently marketed recognize membraneassociated antigens (28,32,37,(71)(72)(73)(74)(75)(76)(77)(78)(79)(80). Interaction of antibodies with this class of target antigen can greatly impact their PK.…”

Section: Introductionmentioning

confidence: 99%

Application of Quantitative Pharmacology in Development of Therapeutic Monoclonal Antibodies

Tabrizi

Funelas

Suria

2010

AAPS J

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Abstract. The advancement of therapeutic monoclonal antibodies during various stages of the drug development process can be effectively streamlined when appropriate translational strategies are applied. Design of successful translational strategies for development of monoclonal antibodies should allow for understanding of the dose-and concentration-response relationships with respect to both beneficial and toxic effects from early phases of drug development. Evaluation of relevant biomarkers during early stages of drug development should facilitate the successful design of safe and effective dosing strategies. Moreover, application of quantitative pharmacology is critical for translation of exposure-response relationships early on.

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“…TGFa, an EGFR ligand under transcriptional control by HIF, is constitutively expressed in VHL mutant cells (Knebelmann et al, 1998;de Paulsen et al, 2001;Gunaratnam et al, 2003). These observations have led to clinical trials of EGFR inhibitors in RCC (Drucker et al, 2003;Motzer et al, 2003;Foon et al, 2004;Rowinsky et al, 2004;Amato, 2005). However, as single -agents, the response rates have been low although stable disease may be prolonged.…”

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confidence: 99%

Synergistic growth inhibition by Iressa and Rapamycin is modulated by VHL mutations in renal cell carcinoma

et al. 2005

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Epidermal growth factor receptor (EGFR) and tumour growth factor alpha (TGFa) are frequently overexpressed in renal cell carcinoma (RCC) yet responses to single-agent EGFR inhibitors are uncommon. Although von Hippel -Lindau (VHL) mutations are predominant, RCC also develops in individuals with tuberous sclerosis (TSC). Tuberous sclerosis mutations activate mammalian target of rapamycin (mTOR) and biochemically resemble VHL alterations. We found that RCC cell lines expressed EGFR mRNA in the near-absence of other ErbB family members. Combined EGFR and mTOR inhibition synergistically impaired growth in a VHLdependent manner. Iressa blocked ERK1/2 phosphorylation specifically in wt-VHL cells, whereas rapamycin inhibited phospho-RPS6 and 4E-BP1 irrespective of VHL. In contrast, phospho-AKT was resistant to these agents and MYC translation initiation (polysome binding) was similarly unaffected unless AKT was inhibited. Primary RCCs vs cell lines contained similar amounts of phospho-ERK1/2, much higher levels of ErbB-3, less phospho-AKT, and no evidence of phospho-RPS6, suggesting that mTOR activity was reduced. A subset of tumours and cell lines expressed elevated eIF4E in the absence of upstream activation. Despite similar amounts of EGFR mRNA, cell lines (vs tumours) overexpressed EGFR protein. In the paired cell lines, PRC3 and WT8, EGFR protein was elevated posttranscriptionally in the VHL mutant and EGF-stimulated phosphorylation was prolonged. We propose that combined EGFR and mTOR inhibitors may be useful in the subset of RCCs with wt-VHL. However, apparent differences between primary tumours and cell lines require further investigation.

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Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody

Abstract: The epidermal growth factor receptor (EGFR) is

Cited by 207 publications

References 28 publications

Novel antibodies as anticancer agents

Novel antibodies as anticancer agents

Application of Quantitative Pharmacology in Development of Therapeutic Monoclonal Antibodies

Synergistic growth inhibition by Iressa and Rapamycin is modulated by VHL mutations in renal cell carcinoma

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