Monoclonal Antibody-Mediated Tumor Regression by Induction of Apoptosis

Abstract

To characterize cell surface molecules involved in control of growth of malignant lymphocytes, monoclonal antibodies were raised against the human B lymphoblast cell line SKW6.4. One monoclonal antibody, anti-APO-1, reacted with a 52-kilodalton antigen (APO-1) on a set of activated human lymphocytes, on malignant human lymphocyte lines, and on some patient-derived leukemic cells. Nanogram quantities of anti-APO-l completely blocked proliferation of cells bearing APO- polyacrylamide gel electrophoresis (SDS-PAGE) as a main band of 52 kD (Fig. 1). Apart from actin (43 kD), which was nonspecifically precipitated with IgG3, anti-APO-1 specifically immunoprecipitated a minor band of 25 kD. This 25-kD protein might either represent a degradation product or be noncovalently associated with the 52-kD protein.There are two major modes of death in nucleated eukaryotic cells. Necrosis as a result, for example, of complement attack is characterized by swelling of the cells and rupture of the plasma membrane caused by an increase in permeability. Cells that undergo apoptosis, however, show a different biochemical and morphological pattern (2). This pattern corresponds to the one induced by anti-APO-1: condensation of the cytoplasm, membrane blebbing (Fig. 2a) (1988). 18. DNA fragments without GREs were inserted into the Xba I site (see Fig. 2) of -33 GRE6, displacing the GRE cassette to -262, -366, and -1069 bp from the start of transcription. Weak receptor-mediated activation was detected when GREs were situated at -262, but no effect was observed from the more distal sites.

In vitro generated human memory‐like T cells are CD95 type II cells and resistant towards CD95‐mediated apoptosis

“…Anti-APO-1 (anti-CD95) was described previously [45]. The hybridomas secreting OKT3, anti-CD28 and I2DIII, were kindly provided by G. Moldenhauer, DKFZ, Heidelberg.…”

Resistance to Fas-mediated apoptosis: activation of Caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP

“…Trauth et al, 1989) transduces the intracellular apoptotic death signaling upon stimulation by Fas ligand (Itoh et al, 1991;Suda et al, 1993;Nagata and Golstein, 1995). Fas plays a dominant role in various physiological cell death and disease states (Nagata and Golstein, 1995;Suzuki et al, 1996a ± c).…”

T-cell development of resistance to apoptosis is driven by a metabolic shift in carbon source and altered activation of death pathways

“…However, in various human disease states, including neurodegeneration, autoimmunity, and cancer, a deregulation or malfunction of this inherent program occurs and cells may develop resistance to apoptosis. 5,6 Apoptosis occurs through two main signaling pathways: an extrinsic pathway that utilizes a diversified group of cell surface death receptors; [7][8][9][10][11][12][13][14] and an intrinsic pathway that utilizes various intracellular organelles to execute the programmed cell death machinery. [15][16][17][18][19][20] An important and well-studied point of control for both the extrinsic and intrinsic apoptotic pathways is the Bcl-2 family of proteins that comprise both pro-and antiapoptotic members and regulate the apoptotic program through a tightly controlled series of checks and balances.…”