Panitumumab

Saltz, Leonard B.; Easley, Chris; Kirkpatrick, Peter

doi:10.1038/nrd2204

Cited by 65 publications

(41 citation statements)

References 11 publications

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“…There are now three antibodies approved by the US FDA for treatment of advanced colorectal cancer (CRC) (Goldberg, 2005;Saltz et al, 2006;Reichert and Valge-Archer, 2007). The main potential advantages of this form of therapy lie in their specificity, lesser side-effects and their ability to elicit a tumour response by multiple mechanisms (Carter, 2006;Reichert and Valge-Archer, 2007).…”

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confidence: 99%

“…The antibodies now used for the treatment of CRC target EGFR and VEGF (Cunningham et al, 2004;Adams and Weiner, 2005;Goldberg, 2005;Carter, 2006;Saltz et al, 2006) and only appear to be effective in subsets of patients. Earlier work from our laboratory has shown that the antibody PR1A3, which is specific for membrane-bound carcinoembryonic antigen (CEA, formally designated CEACAM5), elicits ADCC against CEA-positive CRC cell lines even in the presence of super-physiological levels of free CEA (Durbin and Bodmer, 1987;Durbin et al, 1994;Conaghan et al, 2008).…”

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confidence: 99%

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Humanised IgG1 antibody variants targeting membrane-bound carcinoembryonic antigen by antibody-dependent cellular cytotoxicity and phagocytosis

Ashraf

Umaña²,

Mössner³

et al. 2009

Br J Cancer

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BACKGROUND: The effect of glycoengineering a membrane specific anti-carcinoembryonic antigen (CEA) (this paper uses the original term CEA for the formally designated CEACAM5) antibody (PR1A3) on its ability to enhance killing of colorectal cancer (CRC) cell lines by human immune effector cells was assessed. In vivo efficacy of the antibody was also tested. METHODS: The antibody was modified using EBNA cells cotransfected with b-1,4-N-acetylglucosaminyltransferase III and the humanised hPR1A3 antibody genes. RESULTS: The resulting alteration of the Fc segment glycosylation pattern enhances the antibody's binding affinity to the FcgRIIIa receptor on human immune effector cells but does not alter the antibody's binding capacity. Antibody-dependent cellular cytotoxicity (ADCC) is inhibited in the presence of anti-FcgRIII blocking antibodies. This glycovariant of hPR1A3 enhances ADCC 10-fold relative to the parent unmodified antibody using either unfractionated peripheral blood mononuclear or natural killer (NK) cells and CEA-positive CRC cells as targets. NK cells are far more potent in eliciting ADCC than either freshly isolated monocytes or granulocytes. Flow cytometry and automated fluorescent microscopy have been used to show that both versions of hPR1A3 can induce antibody-dependent cellular phagocytosis (ADCP) by monocyte-derived macrophages. However, the glycovariant antibody did not mediate enhanced ADCP. This may be explained by the relatively low expression of FcgRIIIa on cultured macrophages. In vivo studies show the efficacy of glycoengineered humanised IgG1 PR1A3 in significantly improving survival in a CRC metastatic murine model. CONCLUSION: The greatly enhanced in vitro ADCC activity of the glycoengineered version of hPR1A3 is likely to be clinically beneficial.

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confidence: 99%

mentioning

confidence: 99%

Humanised IgG1 antibody variants targeting membrane-bound carcinoembryonic antigen by antibody-dependent cellular cytotoxicity and phagocytosis

Ashraf

Umaña²,

Mössner³

et al. 2009

Br J Cancer

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“…These include small cell-permeant chemicals that inhibit the tyrosine kinase activity of the receptor, like erlotinib and gefinitib, [54][55][56] as well as the anti-EGFR mAbs cetuximab and panitumumab ( Table 2), which block ligand-induced EGFR activation. 57,58 Necitumumab shares this latter mechanism of action with cetuximab and panitumumab, and it has been shown to be well tolerated by patients and to achieve biologically relevant concentrations throughout the dosing period. 59 Now, necitumumab is being evaluated in two distinct phase III trials for its efficiency against NSCLC, in combination with cisplatin (a DNAdamaging agent) and either gemcitabine (a nucleoside analog) or pemetrexed (an antimetabolite) ( Table 3, NCT00981058 and NCT00982111, respectively).…”

Section: Monoclonal Antibodies Under Advanced (Phase Iii-iv) Clinicalmentioning

confidence: 99%

Trial Watch: Monoclonal antibodies in cancer therapy

et al. 2012

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“…Additionally, Kras is a small G-protein and is significantly involved in signal transduction of the epidermal growth factor receptor (EGFR) and it has been demonstrated that anti-EGFR drugs (Saltz et al 2006), such as panitumumab and cetuximab are ineffective, when K-ras mutations isolate the pathway from providing a target (Alymani et al 2010). Identification of the K-ras mutation can therefore be utilised to identify patients who will not benefit from EGFR inhibitors and may require alternative treatment, as seen in NICE guidance for the treatment of metastatic colorectal cancer (NICE, 2013).…”

Section: Biomarkersmentioning

confidence: 99%

Bioinformatic Analysis for the Validation of Novel Biomarkers for Cancer Diagnosis and Drug Sensitivity

Lockwood¹

2015

Fields: Journal of Huddersfield Student Research

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Background: The genetic control of tumour progression presents the opportunity for bioinformatics and gene expression data to be used as a basis for tumour grading. The development of a genetic signature based on microarray data allows for the development of personalised chemotherapeutic regimes. Method: ONCOMINE was utilised to create a genetic signature for ovarian serous adenocarcinoma and to compare the expression of genes between normal ovarian and cancerous cells. Ingenuity Pathways Analysis was also utilised to develop molecular pathways and observe interactions with exogenous molecules. Results:The gene signature demonstrated 98.6% predictive capability for the differentiation between borderline ovarian serous neoplasm and ovarian serous adenocarcinoma. The data demonstrated that many genes were related to angiogenesis. Thymidylate synthase, GLUT-3 and HSP90AA1 were related to tanespimycin sensitivity (p=0.005). Conclusions: Genetic profiling with the gene signature demonstrated potential for clinical use. The use of tanespimycin alongside overexpression of thymidylate synthase, GLUT-3 and HSP90AA1 is a novel consideration for ovarian cancer treatment.

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Panitumumab

Cited by 65 publications

References 11 publications

Humanised IgG1 antibody variants targeting membrane-bound carcinoembryonic antigen by antibody-dependent cellular cytotoxicity and phagocytosis

Humanised IgG1 antibody variants targeting membrane-bound carcinoembryonic antigen by antibody-dependent cellular cytotoxicity and phagocytosis

Trial Watch: Monoclonal antibodies in cancer therapy

Bioinformatic Analysis for the Validation of Novel Biomarkers for Cancer Diagnosis and Drug Sensitivity

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