RGD Reference Report - Anti-alphav integrin monoclonal antibody intetumumab enhances the efficacy of radiation therapy and reduces metastasis of human cancer xenografts in nude rats.

General

Anti-alphav integrin monoclonal antibody intetumumab enhances the efficacy of radiation therapy and reduces metastasis of human cancer xenografts in nude rats.
Authors:	Ning, Shoucheng Tian, Junqiang Marshall, Deborah J Knox, Susan J
Citation:	Ning S, etal., Cancer Res. 2010 Oct 1;70(19):7591-9. doi: 10.1158/0008-5472.CAN-10-1639. Epub 2010 Sep 14.
RGD ID:	152998949
Pubmed:	PMID:20841470 (View Abstract at PubMed)
DOI:	DOI:10.1158/0008-5472.CAN-10-1639 (Journal Full-text)
We previously reported that intetumumab (CNTO 95), a fully human anti-αv integrin monoclonal antibody, is a radiosensitizer in mice with xenograft tumors. Because intetumumab does not cross-react with mouse integrins, but has cross-reactivity with rat integrins, we next studied the potential combined use of radiation therapy and intetumumab in human cancer xenograft models in nude rats to assess effects on both tumor cells and the tumor microenvironment. Nude rats bearing human head and neck cancer and non-small cell lung cancer (NSCLC) xenografts were treated with intetumumab and fractionated local tumor radiotherapy. Effects on tumor growth and metastasis, blood perfusion, oxygenation, and gastrointestinal toxicity were studied. Intetumumab alone had a moderate effect on tumor growth. When combined with fractionated radiation therapy, intetumumab significantly inhibited tumor growth and produced a tumor response rate that was significantly better than with radiation therapy alone. Treatment with intetumumab also significantly reduced lung metastasis in the A549 NSCLC xenograft model. The oxygenation and blood perfusion in xenograft tumors measured by microbubble-enhanced ultrasound imaging were substantially increased after treatment with intetumumab. The combined use of intetumumab and radiation therapy reduced the microvessel density and increased apoptosis in tumor cells and the tumor microenvironment. Toxicity studies showed that treatment with intetumumab did not cause the histopathologic changes in the lungs and did not sensitize the sensitive gastrointestinal epithelium to the effect of radiation therapy. Intetumumab can potentiate the efficacy of fractionated radiation therapy in human cancer xenograft tumors in nude rats without increased toxicity.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Experimental Neoplasms	treatment	IMP		152998949	human cells in rat model	RGD
Experimental Neoplasms	treatment	ISO	ITGAV (Homo sapiens)	152998949; 152998949	human cells in rat model	RGD
lung metastasis	treatment	IMP		152998949	human cells in rat model	RGD
lung metastasis	treatment	ISO	ITGAV (Homo sapiens)	152998949; 152998949	human cells in rat model	RGD

Objects Annotated

Genes (Rattus norvegicus)

Itgav (integrin subunit alpha V)

Genes (Mus musculus)

Itgav (integrin alpha V)

Genes (Homo sapiens)

ITGAV (integrin subunit alpha V)

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Anti-alphav integrin monoclonal antibody intetumumab enhances the efficacy of radiation therapy and reduces metastasis of human cancer xenografts in nude rats.