Publications by authors named "R E Siebenlist"

A promising strategy for cancer treatment is adoptive gene therapy/immunotherapy by genetically modifying T cells with a chimeric T cell receptor (cTCR). When transduced T cells (T-bodies) specifically bind to tumor antigens through cTCR, they will become cytotoxic T lymphocytes (CTL) and lyse the tumor cells in a non-major histocompatibility complex (MHC)-restricted manner. Both the FcR gamma-chain and the TCR zeta-chain have been used to construct such cTCR, and both have shown specific cytolytic functions against tumor cells.

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Purpose: Effector T cell populations generated using 2 methods of in vitro activation are currently being tested in separate clinical trials as immunotherapy for patients with advanced cancer, including renal cell carcinoma. To determine the most appropriate method of activation for cancer immunotherapy in vitro antitumor activity of the 2 effector T-cell populations were compared.

Methods And Methods: The effector T-cell populations were generated concurrently by activation of peripheral blood mononuclear cells from patients with advanced renal cell carcinoma or other cancer using soluble anti-CD3 monoclonal antibody (3T cells) or anti-CD3 and anti-CD28 monoclonal antibodies immobilized on beads (3/28T cells).

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Relapse after adjuvant chemotherapy or high-dose chemotherapy with stem cell transplant for high-risk breast cancer remains high and new strategies that provide additional antitumor effects are needed. This report describes methods to generate highly effective HER2/neu-specific cytotoxic T cells by arming activated T cells with anti-CD3 x anti-HER2/neu bispecific antibody (BsAb). OKT3 and 9184 (anti-HER2) monoclonal antibodies (mAb) were conjugated and used to arm T cells that were subsequently tested in binding, cytotoxicity, and cytokine secretion assays.

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This report describes the generation of T cells with characteristics that may prove useful for the immunotherapy of cancer. Peripheral blood mononuclear cells obtained from healthy donors were cultured in the presence of anti-CD3/anti-CD28 mAb-coated beads (3/28 beads) at a 3:1 bead to cell ratio. The 3/28 beads were removed after 14 days of culture.

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As an initial step in characterizing the function of basal lamina components during muscle cell differentiation and innervation in vivo, we have determined immunohistochemically the pattern of expression of three components--laminin, proteins related to agrin (an acetylcholine receptor (AChR)-aggregating protein), and a heparan sulfate proteoglycan--during the development of chick embryo hindlimb muscles. Monoclonal antibodies against agrin were used to purify the protein from the Torpedo ray and to characterize agrin-like proteins from embryonic and adult chicken. In early hindlimb buds (stage 19), antibodies against laminin and agrin stained the ectodermal basement membrane and bound to limb mesenchyme with a generalized, punctate distribution.

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