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Cooperative Effect of Radioimmunotherapy and Antiangiogenic Therapy with Thalidomide in Human Cancer Xenografts

¹ Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
² Department of Molecular and Cellular Pathology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
³ Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
⁴ Department of Radiology, Toyama Medical and Pharmaceutical University, Toyama, Japan
⁵ Department of Radiology, Asahikawa Medical College, Asahikawa, Japan
⁶ Medical Informatics, Kanazawa University Hospital, Kanazawa, Japan

Antiangiogenic therapy may prolong the dormancy of cancer lesions. Moreover, radioimmunotherapy (RIT) may eradicate this population of cells. This study dealt with determining the benefits associated with the combined usefulness of these 2 therapies with respect to inhibition of tumor growth. Methods: Antiangiogenic therapy using oral thalidomide (daily dose, 200 mg/kg) and RIT involving a single intravenous injection (4.63 MBq ¹³¹I-A7, an IgG1 murine monoclonal antibody) were conducted in mice bearing LS180 human colon cancer xenografts. RIT with an irrelevant IgG1, HPMS-1, was also performed as a control. Antiangiogenesis of thalidomide was investigated by immunohistochemical analysis of tumor sections. Results: Antiangiogenic therapy and RIT with ¹³¹I-A7 significantly suppressed the growth of xenografts. This combination produced more efficient tumor growth inhibition than did the monotherapy (P < 0.005). RIT using ¹³¹I-HPMS-1 was far less effective than ¹³¹I-A7, even when combined with thalidomide administration. Immunohistochemistry revealed a decrease in the microvessel number within tumors treated with thalidomide (P < 0.0001). Combined therapy further reduced the microvessel number (P < 0.01 vs. thalidomide monotherapy). Conclusion: The combination of RIT and thalidomide antiangiogenic therapy produces a better response of tumors than does monotherapy. Acting in concert, antiangiogenic therapy may prolong the dormancy of cancer lesions and RIT may eradicate this population of cells.

Key Words: radioimmunotherapy • antiangiogenic therapy • thalidomide

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