By a News Reporter-Staff News Editor at Health & Medicine Week -- Investigators publish new report on Mononuclear Leukocytes. According to news reporting originating from Lund, Sweden, by NewsRx correspondents, research stated, "The T lymphocytes are the most important effector cells in immunotherapy of cancer. The conceptual objective for developing the tumor targeted superantigen (TTS) ABR-217620 (naptumomab estafenatox, 5T4Fab-SEA/E-120), now in phase 3 studies for advanced renal cell cancer, was to selectively coat tumor cells with cytotoxic T lymphocytes (CTL) target structures functionally similar to natural CTL pMHC target molecules."
Our news editors obtained a quote from the research from Active Biotech, "Here we present data showing that the molecular basis for the anti-tumor activity by ABR-217620 resides in the distinct interaction between the T cell receptor ? variable (TRBV) 7-9 and the engineered superantigen (Sag) SEA/E-120 in the fusion protein bound to the 5T4 antigen on tumor cells. Multimeric but not monomeric ABR-217620 selectively stains TRBV7-9 expressing T lymphocytes from human peripheral blood similar to antigen specific staining of T cells with pMHC tetramers. SEA/E-120 selectively activates TRBV7-9 expressing T lymphocytes resulting in expansion of the subset. ABR-217620 selectively triggers TRBV7-9 expressing cytotoxic T lymphocytes to kill 5T4 positive tumor cells. Furthermore, ABR-217620 activates TRBV7-9 expressing T cell line cells in the presence of cell-and bead-bound 5T4 tumor antigen. Surface plasmon resonance analysis revealed that ABR-217620 binds to 5T4 with high affinity, to TRBV7-9 with low affinity and to MHC class II with very low affinity. The T lymphocyte engagement by ABR-217620 is constituted by displaying high affinity binding to the tumor cells (KD approximately 1 nM) and with the mimicry of natural productive immune TCR-pMHC contact using affinities of around 1 M."
According to the news editors, the research concluded: "This difference in kinetics between the two components of the ABR-217620 fusion protein will bias the binding towards the 5T4 target antigen, efficiently activating T-cells via SEA/E-120 only when presented by the tumor cells."
For more information on this research see: The tumor targeted superantigen ABR-217620 selectively engages TRBV7-9 and exploits TCR-pMHC affinity mimicry in mediating T cell cytotoxicity. Plos One, 2013;8(10):e79082. (Public Library of Science - www.plos.org; Plos One - www.plosone.org)
The news editors report that additional information may be obtained by contacting G. Hedlund, Active Biotech AB, Lund, Sweden. Additional authors for this research include H. Eriksson, A. Sundstedt, G. Forsberg, B.K. Jakobsen, N. Pumphrey, K. Rodstrom, K. Lindkvist-Petersson and P. Bjork (see also Mononuclear Leukocytes).
Keywords for this news article include: Lund, Sweden, Europe, Immunology, Blood Cells, Superantigens, Mononuclear Leukocytes, Cytotoxic T Lymphocytes, Hemic and Immune Systems, CD8 Positive T Lymphocytes, Cytokine Induced Killer Cells.
Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC