Monoclonal antibody-mediated tumor regression by induction of apoptosis was demonstrated in a study involving the human B lymphoblast cell line SKW6.4. A monoclonal antibody, anti-APO-1, reacted with a 52-kilodalton antigen (APO-1) on activated human lymphocytes, malignant lymphocyte lines, and some patient-derived leukemic cells. Nanogram quantities of anti-APO-1 completely blocked proliferation of cells bearing APO-1 in vitro, a process characteristic of programmed cell death or apoptosis. Cell death was preceded by morphological changes and DNA fragmentation. This process was distinct from antibody- and complement-dependent cell lysis and was mediated by the antibody alone. A single intravenous injection of anti-APO-1 into nu/nu mice carrying a xenotransplant of a human B cell tumor induced regression of this tumor within a few days. Histological thin sections of the regressing tumor showed that anti-APO-1 was able to induce apoptosis in vivo. Thus, induction of apoptosis as a consequence of a signal mediated through cell surface molecules like APO-1 may be a useful therapeutic approach in treatment of malignancy. Cell surface molecules are crucial in lymphocyte growth control. Such molecules may function as receptors for growth-stimulating cytokines or be associated with receptors and transmit signals essential for growth regulation. Receptor blockade or removal of the stimulating cytokines can lead to decreased lymphocyte growth. Withdrawal of interleukin slow human lymphocyte growth and finally leads to a characteristic form of cell death called "programmed cell death" or apoptosis. Apoptosis is the most common form of eukaryotic cell death and occurs in embryogenesis, metamorphosis, tissue atrophy, and tumor regression. It is also induced by cytotoxic T lymphocytes and natural killer and killer cells; by cytokines like tumor necrosis factor (TNF) and lymphotoxin (LT); and by glucocorticoids. The most characteristic signs of apoptosis are segmentation of the nucleus, condensation of the cytoplasm, membrane blebbing, and DNA fragmentation into multimers of about 180 base pairs (called a "DNA ladder"). To analyze mechanisms of lymphocyte growth control and to interfere with the replication of lymphoid tumor cells, monoclonal antibodies (MAbs) against cell surface molecules involved in these processes were raised. One MAb (anti-APO-1) was found to block growth and induce apoptosis of SKW6.4 cells. Anti-APO-1 bound to approximately 4×10^4 sites on the surface of SKW6.4 cells and specifically immunoprecipitated an endogenously synthesized protein antigen (APO-1) from SKW6.4 cells. APO-1 was observed on SDS-PAGE as a main band of 52 kD. Apart from actin (43 kD),Monoclonal antibody-mediated tumor regression by induction of apoptosis was demonstrated in a study involving the human B lymphoblast cell line SKW6.4. A monoclonal antibody, anti-APO-1, reacted with a 52-kilodalton antigen (APO-1) on activated human lymphocytes, malignant lymphocyte lines, and some patient-derived leukemic cells. Nanogram quantities of anti-APO-1 completely blocked proliferation of cells bearing APO-1 in vitro, a process characteristic of programmed cell death or apoptosis. Cell death was preceded by morphological changes and DNA fragmentation. This process was distinct from antibody- and complement-dependent cell lysis and was mediated by the antibody alone. A single intravenous injection of anti-APO-1 into nu/nu mice carrying a xenotransplant of a human B cell tumor induced regression of this tumor within a few days. Histological thin sections of the regressing tumor showed that anti-APO-1 was able to induce apoptosis in vivo. Thus, induction of apoptosis as a consequence of a signal mediated through cell surface molecules like APO-1 may be a useful therapeutic approach in treatment of malignancy. Cell surface molecules are crucial in lymphocyte growth control. Such molecules may function as receptors for growth-stimulating cytokines or be associated with receptors and transmit signals essential for growth regulation. Receptor blockade or removal of the stimulating cytokines can lead to decreased lymphocyte growth. Withdrawal of interleukin slow human lymphocyte growth and finally leads to a characteristic form of cell death called "programmed cell death" or apoptosis. Apoptosis is the most common form of eukaryotic cell death and occurs in embryogenesis, metamorphosis, tissue atrophy, and tumor regression. It is also induced by cytotoxic T lymphocytes and natural killer and killer cells; by cytokines like tumor necrosis factor (TNF) and lymphotoxin (LT); and by glucocorticoids. The most characteristic signs of apoptosis are segmentation of the nucleus, condensation of the cytoplasm, membrane blebbing, and DNA fragmentation into multimers of about 180 base pairs (called a "DNA ladder"). To analyze mechanisms of lymphocyte growth control and to interfere with the replication of lymphoid tumor cells, monoclonal antibodies (MAbs) against cell surface molecules involved in these processes were raised. One MAb (anti-APO-1) was found to block growth and induce apoptosis of SKW6.4 cells. Anti-APO-1 bound to approximately 4×10^4 sites on the surface of SKW6.4 cells and specifically immunoprecipitated an endogenously synthesized protein antigen (APO-1) from SKW6.4 cells. APO-1 was observed on SDS-PAGE as a main band of 52 kD. Apart from actin (43 kD),