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Vinay D.S.,Tulane University | Kwon B.S.,Tulane University | Kwon B.S.,Cell Therapeutics
Molecular Cancer Therapeutics

4-1BB (CD137), a member of the TNF receptor superfamily, is an activation-induced T-cell costimulatory molecule. Signaling via 4-1BB upregulates survival genes, enhances cell division, induces cytokine production, and prevents activation-induced cell death in T cells. The importance of the 4-1BB pathway has been underscored in a number of diseases, including cancer. Growing evidence indicates that anti-4-1BB monoclonal antibodies possess strong antitumor properties, which in turn are the result of their powerful CD8+ T-cell activating, IFN-γ producing, and cytolytic marker-inducing capabilities. In addition, combination therapy of anti-4-1BB with other anticancer agents, such as radiation, has robust tumor-regressing abilities against nonimmunogenic or poorly immunogenic tumors. Furthermore, the adoptive transfer of ex vivo anti-4-1BB-activated CD8+ T cells from previously tumor-treated animals efficiently inhibits progression of tumors in recipient mice that have been inoculated with fresh tumors. In addition, targeting of tumors with variants of 4-1BBL directed against 4-1BB also have potent antitumor effects. Currently, a humanized anti-4-1BB is in clinical trials in patients with solid tumors, including melanoma, renal carcinoma, and ovarian cancer, and so far seems to have a favorable toxicity profile. In this review, we discuss the basis of the therapeutic potential of targeting the 4-1BB-4-1BBL pathway in cancer treatment. ©2012 AACR. Source

Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (EDTA-PTCP) is a well known phenomenon. Antiplatelet antibodies cause platelet clumping in EDTA anticoagulated blood samples, and blood count analysers calculate a spurious low platelet count. We describe a case of a transient appearance of EDTA-PTCP in a patient after gastrectomy. A 58-year-old man underwent partial gastrectomy in for gastric cancer. Preoperatively, his platelet count was in a normal range, and the surgical procedure was performed without bleeding complications. At day 10 after surgery the patient showed a low platelet count, which could be identified as EDTA-PTCP. The phenomenon disappeared in a following postoperative time interval of 2 months. In cases of recently occurring thrombocytopenias EDTA-PTCP should always be considered as a possible cause of low platelet count, in particular in cases of inconspicuous clinical findings. Appropriate laboratory analysis should be applied. Source

Bonig H.,University of Washington | Bonig H.,Cell Therapeutics | Papayannopoulou T.,University of Washington

Despite its specific clinical relevance, the field of hematopoietic stem cell mobilization has received broad attention, owing mainly to the belief that pharmacologic stem cell mobilization might provide clues as to how stem cells are retained in their natural environment, the bone marrow 'niche'. Inherent to this knowledge is also the desire to optimally engineer stem cells to interact with their target niche (such as after transplantation), or to lure malignant stem cells out of their protective niches (in order to kill them), and in general to decipher the niche's structural components and its organization. Whereas, with the exception of the recent addition of CXCR4 antagonists to the armamentarium for mobilization of patients refractory to granulocyte colony-stimulating factor alone, clinical stem cell mobilization has not changed significantly over the last decade or so, much effort has been made trying to explain the complex mechanism(s) by which hematopoietic stem and progenitor cells leave the marrow. This brief review will report some of the more recent advances about mobilization, with an attempt to reconcile some of the seemingly inconsistent data in mobilization and to interject some commonalities among different mobilization regimes. © 2013 Macmillan Publishers Limited All rights reserved. Source

The invention relates to an improved process for the preparation of poly--glutamic acids which comprises the polymerization of tertiary -esters of -glutamic acid N-carboxy anhydride with appropriate solvents and initiators, followed by acid hydrolysis of the resulting poly--glutamic acid--ester. The process is particularly advantageous in that it allows one to carefully control the molecular weight of the resulting poly--glutamic acid. The invention also relates to poly--glutamic acids capped at the amino terminus with carboxylic acids or amino acids and to a process for the preparation thereof.

The present invention relates to the chromatographic isolation of a target cell or another complex biological material, in particular by column chromatography such as affinity chromatography or gel permeation chromatography. The invention employs a receptor binding reagent that binds to a receptor molecule that is located on the surface of a target cell. The invention in general provides novel methods for the traceless isolation of biologic materials such as cells, cell organelles, viruses and the like. The invention also relates to an apparatus for the isolation of cells and other complex biological materials.

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