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Assessment of Biological Activity of Linear -Transforming Growth Factor and Monospecific Antibodies to -Transforming Growth Factor and Linear -Transforming Growth Factor¹

Department of Medicine, Division of Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284 [A.-R. H., J. B. B., V. A. M., D. D. V. H.]; Department of Medicine, University of Texas, Medical School at Houston, Houston, Texas 77030; and Triton Biosciences, Inc., Alameda, California 94501 [R. L. P.]

-Transforming growth factors (TGFs) are low-molecular-weight polypeptides (M_r 5000–7000) which are secreted by a variety of human cancer cells in vitro. Their presence has also been reported in the urine of patients with malignancies, human tumor extracts, and in the conditioned medium of primary human tumor cell cultures. There is evidence that -TGFs bind to membrane receptors of the secreting cells, thus stimulating cell growth in a positive feedback manner (autocrine secretion). We have used a synthetic linear -TGF to study the biological activity of affinity-purified polyclonal sheep antibodies against the carboxyterminal part (17 amino acids) of synthetic rat -TGF. The antigen was found to bind to epidermal growth factor receptors of target cells and to stimulate soft agarose colony formation of normal fibroblasts. Although the antibodies recognized the linear -TGF molecule, they did not inhibit the binding to epidermal growth factor receptors. The antibodies also failed to inhibit -TGF-stimulated colony formation of normal rat fibroblasts. In addition, essentially no cytotoxic activity of the antibodies was found against 41 fresh human tumor specimens in a human tumor cloning assay. Antibodies against the complete -TGF molecule should be used in further attempts to interfere with the autocrine secretion of transforming growth factors.

¹ This work has been supported in part by grant CM 27733 from the National Cancer Institute (D. D. V. H.), by grant CH162E from the American Cancer Society, and by grant Ha 1347/1-1 from the Deutsche Forschungsgemeinschaft (A-R. H).

Received 10/17/85. Revised 3/26/86. Revised 7/22/86. Accepted 8/ 5/86.