By a News Reporter-Staff News Editor at Cancer Gene Therapy Week -- Data detailed on Biotechnology have been presented. According to news originating from Memphis, Tennessee, by NewsRx correspondents, research stated, "To expand applications for T-cell-based immunotherapy in cancer, we designed a receptor that binds the Fc portion of human immunoglobulins and delivers activation signals. The construct included the high-affinity CD16 (FCGR3A) V158 variant, CD8 alpha hinge, and transmembrane domains, along with signaling domains from CD3 zeta and 4-1BB (TNFRSF9), forming a chimeric receptor termed CD16V-BB-zeta."
Our news journalists obtained a quote from the research from St. Jude Children's Research Hospital, "After retrovirus-mediated expression in human T cells, CD16V-BB-zeta bound humanized antibodies with higher affinity than a control receptor containing the more common F158 variant. Engagement of CD16V-BB-zeta provoked T-cell activation, exocytosis of lytic granules, and sustained proliferation, with a mean cell recovery after4-week coculture with Daudi lymphoma cells and rituximab of nearly 70-fold relative to input cells. In contrast, unbound antibody alone produced no effect. CD16V-BB-zeta T cells specifically killed lymphoma cells and primary chronic lymphocytic leukemia cells in combination with rituximab at a low effector target ratio, even when assayed on mesenchymal cells. Trastuzumab triggered CD16V-BB-zeta-mediated killing of HER2 (ERBB2)(+) breast and gastric cancer cells; similar results were obtained with an anti-GD2 antibody in neuroblastoma and osteosarcoma cells. Furthermore, coadministration of CD16V-BB-zeta T cells with immunotherapeutic antibodies exerted considerable antitumor activity in vivo. Signaling mediated by 4-1BB-CD3 zeta induced higher T-cell activation, proliferation, and cytotoxicity than CD3 zeta or Fc epsilon RI gamma, and the receptor was expressed effectively after mRNA electroporation without viral vectors, facilitating clinical translation."
According to the news editors, the research concluded: "Our results offer preclinical proof of concept for CD16V-BB-zeta as a universal, next-generation chimeric receptor with the potential to augment the efficacy of antibody therapies for cancer."
For more information on this research see: T Lymphocytes Expressing a CD16 Signaling Receptor Exert Antibody-Dependent Cancer Cell Killing. Cancer Research, 2014;74(1):93-103. Cancer Research can be contacted at: Amer Assoc Cancer Research, 615 Chestnut St, 17TH Floor, Philadelphia, PA 19106-4404, USA. (American Association for Cancer Research - www.aacr.com; Cancer Research - cancerres.aacrjournals.org/)
The news correspondents report that additional information may be obtained from K. Kudo, St Jude Childrens Res Hosp, Dept. of Surg, Memphis, TN 38105, United States. Additional authors for this research include C. Imai, P. Lorenzini, T. Kamiya, K. Kono, A.M. Davidoff, W.J. Chng and D. Campana (see also Biotechnology).
Keywords for this news article include: Antineoplastic Monoclonal Antibodies, Antirheumatics, Biotechnology, Biomedical Engineering, Drugs, Memphis, Oncology, Tennessee, Rituximab, Immunology, Blood Cells, United States, Immunotherapy, T-Lymphocytes, Blood Proteins, Immunoglobulins, Medical Devices, Immunomodulation, Cancer Gene Therapy, Humanized Antibodies
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