TRANSFORMING GROWTH FACTORS (TGFS) CAN INDUCE AND MAINTAIN THE TRANSFORMED PHENOTYPE.

TRANSFORMING GROWTH FACTORS (TGFS) CAN INDUCE AND MAINTAIN THE TRANSFORMED PHENOTYPE. TGFS ARE PRODUCED BY TUMOR CELLS AND CAN ACT ON THOSE TUMOR CELLS (AUTOCRINE EFFECT) OR CAN INDUCE A REVERSIBLE ""TRANSFORMED'' STATE IN NORMAL CELLS, FOR EXAMPLE IN NORMAL RAT KIDNEY (NRK) CELLS GROWN IN SOFT AGAR. TGFS HAVE RECENTLY BEEN PURIFIED AND HAVE BEEN CLASSIFIED AS -TGFS, MEANING EPIDERMAL GROWTH FACTOR-LIKE, OR -TGFS, WHICH REQUIRE EGF FOR FUNCTION. MONOCLONAL ANTIBODIES (MOABS) RAISED AGAINST TGFS MAY COMPETE WITH TGF RECEPTORS FOR THE BINDING OF TGFS AND MAY INHIBIT THE ACTION OF TGFS ON TUMOR OR NORMAL CELLS. THIS PROPOSAL DESCRIBES THE PRODUCTION OF HUMAN MOABS TO - AND -TGFS USING AN IN VITRO IMMUNIZATION PROTOCOL USING DEFINED, SERUM-FREE MEDIUM. PURIFIED TGFS WILL SERVE AS ANTIGEN USING HUMAN PERIPHERAL BLOOD B CELLS. MOUSE-HUMAN AND HUMAN-HUMAN HYBRIDOMAS WILL BE CONSTRUCTED. SCREENING OF MOABS THUS FORMED WILL BE DONE BY THE INHIBITION OF GROWTH OF NRK CELLS IN SOFT AGAR. MOABS AGAINST TGFS WILL HAVE POTENTIAL COMMERCIAL VALUE AS REAGENTS FOR IMMUNOASSAYS FOR TGFS AND MAY HAVE USE IN A CLINICAL SETTING FOR THE INHIBITION OF TUMOR GROWTH IN VIVO.