Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250.

American Society of Clinical Oncology (ASCO) - Tập 11 Số 4 - Trang 738-750 - 1993
Egbert Oosterwijk1, Neil H. Bander2, C R Divgi3, Sydney Welt4, Jeannette C. Wakka5, Ronald D. Finn3, E A Carswell4, Steven M. Larson3, S. O. Warnaar6, Gert Jan Fleuren5
1Ludwig Institute for Cancer Research, New York, NY
2New York Hospital-Cornell University Medical Center, New York, USA
3Memorial Sloan- Kettering Cancer Center, New York, USA
4Ludwig Institute for Cancer Research, New York, USA
5University Hospital Nijmegen, The Netherlands
6Centocor Inc., Philadelphia, USA

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PURPOSE To define the imaging and biodistribution characteristics of iodine 131-labeled monoclonal antibody (mAb) G250 (131I-mAbG250), which recognizes a cell-surface antigen expressed by human renal cell carcinoma (RCC). PATIENTS AND METHODS G250 is a cell-surface antigen recognized by mAbG250 expressed by RCC but not detected in normal kidney. Clear-cell RCC, the most frequent form of RCC, shows homogeneous expression of G250, whereas non-clear-cell RCC and cancers derived from other organs generally do not express G250. Expression in normal tissues is highly restricted and limited to large bile ducts and gastric epithelium. 131I-mAbG250 was administered intravenously (IV) to 16 patients with RCC 7 to 8 days before surgery at five dose levels, with at least three patients entered at each dose level. RESULTS Clear tumor images were observed in 12 patients with G250-positive tumors and in one of three patients with G250-negative tumors. Imaged lesions in the peritoneal cavity were confirmed at surgery. The smallest lesion visualized was 8 mm in diameter. The specificity of 131I-mAbG250 localization to tumor tissue was established by radioactivity measurements, autoradiography, and immunohistochemistry of biopsied tissues, and technetium 99-human serum albumin blood-flow studies. The fraction of the injected 131I-mAbG250 dose per gram tumor (%ID/g tumor) localized in G250-positive tumors showed a broad range, but reached levels as high as 0.02% to 0.12%. CONCLUSION 131I-mAbG250 localized specifically to G250 antigen-positive RCC and seems to have considerable potential as an imaging agent in RCC patients. 131I-mAbG250 uptake in the tumors, relative as well as absolute, are among the highest reported for tumor biopsies obtained 8 days after IV mAb administration. Based on the specific localization and high accumulation, mAb G250 may have therapeutic potential.

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American Society of Clinical Oncology (ASCO)

Tập 11 Số 4

738-750

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