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PURPOSE Glioblastoma multiforme (GBM) is the most aggressive human primary brain tumor and is currently incurable. Immunotherapies have the potential to target GBM stem cells, which are resistant to conventional therapies. Human epidermal growth factor receptor 2 (HER2) is a validated immunotherapy target, and we determined if HER2-specific T cells can be(More)
Cancer-associated fibroblasts (CAFs), the principle component of the tumor-associated stroma, form a highly protumorigenic and immunosuppressive microenvironment that mediates therapeutic resistance. Co-targeting CAFs in addition to cancer cells may therefore augment the antitumor response. Fibroblast activation protein-α (FAP), a type 2 dipeptidyl(More)
Targeted T cells are emerging as effective non-toxic therapies for cancer. Multiple elements, however, contribute to the overall pathogenesis of cancer through both distinct and redundant mechanisms. Hence, targeting multiple cancer-specific markers simultaneously could result in better therapeutic efficacy. We created a functional chimeric antigen(More)
Recent clinical trials showed that targeting of inhibitory receptors on T cells induces durable responses in a subset of cancer patients, despite advanced disease. However, the regulatory switches controlling T-cell function in immunosuppressive tumours are not well understood. Here we show that such inhibitory mechanisms can be systematically discovered in(More)
Outcomes for patients with glioblastoma (GBM) remain poor despite aggressive multimodal therapy. Immunotherapy with genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL)-13Rα2, epidermal growth factor receptor variant III (EGFRvIII), or human epidermal growth factor receptor 2 (HER2) has shown promise for the(More)
BACKGROUND AIMS Hematopoietic stem cell transplant (HSCT) is the treatment of choice for a proportion of patients with hematologic malignancies as well as for non-malignant diseases. However, viral infections, particularly Epstein-Barr virus (EBV), cytomegalovirus (CMV) and adenovirus (Ad), remain problematic after transplant despite the use of antiviral(More)
Interaction between lipoproteins and elastin in the arterial wall may play an important role in atherosclerotic lipid deposition, but binding affinities and other characteristics of the interaction have not been determined previously. Elastin was isolated by hot alkali treatment of human aortic tissue. At 4 degrees C, radioiodinated human low density(More)
An optimized antigen-presenting cell for tumor immunotherapy should produce a robust antigen specific cytotoxic T lymphocytes (CTL) response to tumor-associated antigens, which can persist in vivo and expand on antigen reencounter. Interleukin (IL)-21 synergizes with other gamma-chain cytokines to enhance the frequency and cytotoxicity of antigen-specific(More)
Glioblastoma (GBM) is the most common primary brain cancer in adults and is virtually incurable. Recent studies have shown that cytomegalovirus (CMV) is present in majority of GBMs. To evaluate whether the CMV antigens pp65 and IE1, which are expressed in GBMs, could be targeted by CMV-specific T cells, we measured the frequency of T cells targeting pp65(More)
T-cell therapy with genetically modified T cells targeting CD19 or CD20 holds promise for the immunotherapy of hematologic malignancies. These targets, however, are only present on B cell-derived malignancies, and because they are broadly expressed in the hematopoietic system, their targeting may have unwanted consequences. To expand T-cell therapies to(More)