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Immunotherapy of Human Glioma Xenografts with Unlabeled, ¹³¹I-, or ¹²⁵I-labeled Monoclonal Antibody 425 to Epidermal Growth Factor Receptor¹

The Wistar Institute, Philadelphia, Pennsylvania 19104 [H. B., H. T., K. A., P. B., S. L., M. P., U. R., D. H.], Scripps Clinics, La Jolla, California 92037 [M. S.], and E. Merck, Darmstadt, Federal Republic of Germany [A. S.]

Monoclonal antibody (mAb) 425 (IgG2a) binds to the external domain of the epidermal growth factor receptor. This determinant is highly expressed by human glioma tissues but rarely by normal brain tissues, and is absent on peripheral blood lymphocytes and bone marrow cells. The mAb exerts variable cytotoxic effects against cultured human glioma cells in conjunction with human and murine effector cells. Inhibition of growth of s.c. glioma xenografts in nude mice by the mAb may be mediated by murine macrophages or may be related to the capacity of the mAb to antagonize growth stimulation of glioma cells by epidermal growth factor. In approaches to radioimmunotherapy of human glioma with mAb 425, the ¹²⁵I-labeled mAb 425 exhibited more significant antitumor effects than the ¹³¹I-labeled mAb both in vitro and in vivo in xenotransplanted nude mice. These differences may be due to enhanced nuclear damage caused by ¹²⁵I-labeled versus ¹³¹I-labeled fragments following their internalization into the glioma cells. Our studies provide the rationale for immunotherapy of glioma patients with either unlabeled or ¹²⁵I-labeled anti-epidermal growth factor receptor mAb 425.

¹ These studies were supported by NIH Grant CA-10815; H. B. is the recipient of a fellowship from the Deutsche Forschungsgemeinschaft; H. T. and K. A. are recipients of fellowships from Ajinomoto Company, Japan.

² To whom requests for reprints should be addressed, at the Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104-4268.

Received 5/ 6/91. Accepted 10/18/91.

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