Anti–αv Integrin Monoclonal Antibody Intetumumab Enhances the Efficacy of Radiation Therapy and Reduces Metastasis of Human Cancer Xenografts in Nude Rats英文文献.pdfVIP

Therapeutics, Targets, and Chemical Biology Cancer Research Anti–αv Integrin Monoclonal Antibody Intetumumab Enhances the Efficacy of Radiation Therapy and Reduces Metastasis of Human Cancer Xenografts in Nude Rats 1 1 2 1 Shoucheng Ning , Junqiang Tian , Deborah J. Marshall , and Susan J. Knox Abstract 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 stud- ied. 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 tum