Optimization studies for the coupling of bispecific antibodies to viral anchor molecules of a tumor vaccine
Tumor vaccines have to provide several signals for T cell activation. Among them, signal 1 (through TCR/CD3) and signal 2 (through CD28) are the most important. We herein describe a procedure to introduce anti-CD3 and anti-CD28 signals into any tumor cell which is susceptible to infection by Newcastle disease virus (NDV). We developed the ATV-NDV tumor vaccine which consists of patient-derived tumor cells (ATV) modified through infection by NDV. We tested for further improvement of vaccine efficiency the addition of two bispecific single-chain antibodies. They bind with one arm to the viral hemagglutinin-neuraminidase (HN) or fusion (F) protein of NDV expressed at the surface of the vaccine cells while the second arm is directed either against CD3 or CD28 of T cells. The aim of this study was to optimize the coupling of these new reagents to the tumor vaccine. When anti-CD3 and anti-CD28 molecules bind to the same anchoring viral molecule (e.g. HN), competition for binding could occur under certain conditions. This was not the case when the bispecific reagents bound to separate viral molecules (HN or F, respectively). When using transfectants expressing HN and F either separately or on the same cell, we show that T cell activation works best when anti-CD3 and anti-CD28 are attached to the same stimulator cell. The clinical application of such a combined therapy with ATV-NDV vaccine cells and bi-specific antibodies allows to modify the strength of signal 1 and 2 in a quantitative and predictable way according to the immune status of the T cells and the requirements of the patients' immune system.
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Document Type: Research Article
Affiliations: Tumorimmunology Program, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
Publication date: November 1, 2010
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- The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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