Human monoclonal antibodies to the insulin-like growth factor 1 receptor inhibit receptor activation and tumor growth in preclinical studies

Runnels, Herbert A.; Arbuckle, J. Alan; Bailey, Karen S.; Nicastro, Peter J.; Sun, Dengming; Pegg, Jodi A.; Meyer, Debra M.; Evans, Michelle; Bono, Christine P.; Lie, Wen-Rong; Moffat, Mandy; Casperson, Gerald F.; Lennard, Simon; Elvin, John; Vaughan, Tristan J.; Smith, Christine E.; Morton, Phillip A.

doi:10.1007/s12325-010-0026-5

Cited by 6 publications

(5 citation statements)

References 22 publications

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“…As an example, anti-IGF-1R antibodies were designed to achieve maximum binding to the receptor, with the intention of competing with natural agonists [157]. In the drug screening stages the assays were limited to confirmation of their inhibitory effects on IGF-1 induced receptor tyrosine phosphorylation and PI3K/Akt signalling [16,27,118,119,148]. Because the canonical IGF-1R model does not acknowledge kinaseindependent signalling, these targeting antibodies were rarely evaluated in IGF-1-independent conditions.…”

Section: Discussionmentioning

confidence: 99%

The dichotomy of the Insulin-like growth factor 1 receptor: RTK and GPCR: friend or foe for cancer treatment?

Crudden

Ilić

Suleymanova

et al. 2015

Growth Hormone & IGF Research

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Section: Discussionmentioning

confidence: 99%

The dichotomy of the Insulin-like growth factor 1 receptor: RTK and GPCR: friend or foe for cancer treatment?

Crudden

Ilić

Suleymanova

et al. 2015

Growth Hormone & IGF Research

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“…3b). This was used in a recent study, where antibodies were selected that prevented the interaction of insulin-like growth factor type 1 (IGF-1) with the IGF-1 receptor106. Several groups of receptor binders were generated that competed with ligand binding and blocked cell growth in vitro and in vivo.…”

Section: Antibodies To Cell Surface Receptorsmentioning

confidence: 99%

Beyond natural antibodies: the power of in vitro display technologies

et al. 2011

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In vitro display technologies, best exemplified by phage and yeast display, were first described for the selection of antibodies some twenty years ago. Since that time a large number of antibodies, some with remarkable properties, have been selected and improved upon using these methods. The first antibodies derived using in vitro display methods are now in the clinic, with many more waiting in the wings. Here we discuss the scope of the technology, some of the powerful antibodies selected, and the future potential in a post-genomic world. Unique advantages offered by in vitro display technologies include the ability to carefully define selection conditions, allowing the derivation of antibodies recognizing predefined epitopes or conformations, the further improvement of selected antibodies, the potential for high throughput applications and the immediate availability of genes encoding the selected antibody. We anticipate that the high throughput potential of these technologies will soon lead to their use to select antibodies against all human proteins.

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“…These antibodies, namely IGF-IR antibodies 7A6, 9A2, and 12A1 inhibited (125I)-IGF-I binding, and IGF-IR antibodies 7A4, 8A1, and 9A2 inhibited (125I)-labeled IGF-II binding to NIH-3T3 cells expressing the human IGF-IR. These antibodies exhibited activity against human, primate, and rodent IGF-IRs, and dose-dependently inhibited the growth of established human tumors in nude mice (34). Human mAbs to the IGF-IR were shown to inhibit receptor activation and tumor growth in preclinical studies.…”

Section: Insulin-like Growth Factor I Receptor As a Targetmentioning

confidence: 99%

“…Using a phage display library, several highaffinity fully human mAbs with inhibitory activity against human IGF-IR were identified (34). The candidate therapeutic antibodies recognized several distinct epitopes and effectively blocked ligand-mediated receptor signal transduction and cellular proliferation in vitro.…”

Section: Insulin-like Growth Factor I Receptor As a Targetmentioning

confidence: 99%

Human monoclonal antibodies in cancer therapy: a review of recent developments

Xin

Cao²,

Cheng³

et al. 2013

Front Biosci

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In the last decade, phage-display technology for the generation of monoclonal antibodies (mAbs) has improved significantly. Several novel human mAbs directed to a wide range of targets have been generated for the treatment of common malignancies. These targets include antigens associated with apoptosis, angiogenesis and solid tumors, as well as tumor growth-related antigens, insulin-like growth factor I receptor and hepatocyte growth factor. The safety, pharmacokinetics, and pharmacodynamics of several human mAbs have been evaluated in patients with advanced solid tumors. In conclusion, significant advances in the generation and application of human mAbs in cancer therapy have been made in the last decade.

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Human monoclonal antibodies to the insulin-like growth factor 1 receptor inhibit receptor activation and tumor growth in preclinical studies

Abstract: These fully human antibodies therefore have the potential to provide an effective anti-tumor biological therapy in the human clinical setting.

Cited by 6 publications

References 22 publications

The dichotomy of the Insulin-like growth factor 1 receptor: RTK and GPCR: friend or foe for cancer treatment?

The dichotomy of the Insulin-like growth factor 1 receptor: RTK and GPCR: friend or foe for cancer treatment?

Beyond natural antibodies: the power of in vitro display technologies

Human monoclonal antibodies in cancer therapy: a review of recent developments

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