C. Klas

Bio: C. Klas is an academic researcher from German Cancer Research Center. The author has contributed to research in topics: Apoptosis & Antigen. The author has an hindex of 6, co-authored 8 publications receiving 3272 citations.

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-1 completely blocked proliferation of cells bearing APO-1 in vitro in a manner characteristic of a process called programmed cell death or apoptosis. Cell death was preceded by changes in cell morphology and fragmentation of DNA. 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.

Activation interferes with the APO-1 pathway in mature human T cells

Abstract: One of the mechanisms to terminate a specific immune response may involve elimination of antigen activated T cells by programmed cell death, apoptosis. Apoptosis in activated T cells may be induced via the TCR-CD3 complex or/and cell surface molecules like the APO-1 (Fas) antigen, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily. To investigate apoptosis in activated T cells we studied expression of APO-1 and sensitivity to APO-1 mediated apoptosis in human peripheral T lymphocytes. APO-1 is not expressed on cord blood and the majority of resting T cells, but on activated T cells. One day activated T cells in culture showed activation induced resistance to apoptosis (ARA). However, after prolonged in vitro culture, 6 day activated T cells acquired sensitivity to activation induced sensitivity to apoptosis (ASA). Restimulation of the ASA+ activated T cells by triggering TCR-CD3 or CD2 induced proliferation and apoptosis in a fraction of the cells. In the surviving fraction of ASA+ activated T cells, however, this treatment reinduced a transient ARA+ phenotype. Thus, activation of resting mature T cells or restimulation of activated T cells may induce a transient resistance to apoptotic signals. Activation signals may interfere with the APO-1 pathway and may prevent elimination of activated T cells in the periphery (peripheral selection).

Apoptosis in the Apo-1 system

Abstract: P.H. Krommert I. Behrmann,] V. Bier,2 P. Don/e/,1 J. Dhein,] M.H. FcrWc,3 G. Gcrrc/n,1 C . K/as,1 E. Knipping,] K.-M. Lücking-Famira,] S. Matzku* A. Oehm,] S. Richards,] B.C. Trauth,] G.W. Bornkamm,3 W. Falk,] P. Möller* and K.-M. Debatin2 institute for Immunology and Genetics, German Cancer Research Center, Heidelberg, Germany 2Children's Hospital, University of Heidelberg, Germany ^Institute for Clinical Molecular Biology/GSF, Munich, Germany ^Institute for Radiobiology and Pathophysiology, German Cancer Research Center, Heidelberg, Germany ^Institute for Pathology, University of Heidelberg, Germany

The Fas Death Factor

Abstract: Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells. Various cells express Fas, whereas FasL is expressed predominantly in activated T cells. In the immune system, Fas and FasL are involved in down-regulation of immune reactions as well as in T cell-mediated cytotoxicity. Malfunction of the Fas system causes lymphoproliferative disorders and accelerates autoimmune diseases, whereas its exacerbation may cause tissue destruction.