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PURPOSE A phase I study was conducted to assess the safety of adoptive immunotherapy using gene-modified autologous T cells for the treatment of metastatic ovarian cancer. EXPERIMENTAL DESIGN T cells with reactivity against the ovarian cancer-associated antigen alpha-folate receptor (FR) were generated by genetic modification of autologous T cells with a(More)
To gain ample numbers of dendritic cells (DCs) for investigation, or for immunotherapy, the culture of DC precursors from bone marrow in either GM-CSF and IL-4 (GM/IL4-DCs) or Flt3L (FL-DCs) has often been used. Despite their common use, the relationship of these culture-derived DCs to those in vivo, and their relative potential for use in immunotherapy,(More)
PURPOSE To determine the antitumor efficacy and toxicity of a novel combination approach involving adoptive T-cell immunotherapy using chimeric antigen receptor (CAR) T cells with an immunomodulatory reagent for blocking immunosuppression. EXPERIMENTAL DESIGN We examined whether administration of a PD-1 blocking antibody could increase the therapeutic(More)
The major limiting factor in the successful application of adjuvant therapy for metastatic disease is the lack of adjuvant specificity that leads to severe side effects. Reasoning that T cells of the immune system are highly specific, we generated tumor-specific T cells by genetic modification of mouse primary T cells with a chimeric receptor reactive with(More)
Immunotherapies are emerging as highly promising approaches for the treatment of cancer. In these approaches, a variety of materials are used to boost immunity against malignant cells. A key component of many of these approaches is functional tumor-specific T cells, but the existence and activity of sufficient T cells in the immune repertoire is not always(More)
NKG2D is an activation receptor on NK cells and has been demonstrated as a primary cytotoxicity receptor for mouse NK cells. Primary rejection of class I-deficient RMA-S lymphoma cells expressing the NKG2D ligand, retinoic acid early inducible-1beta, was critically dependent upon NK cell perforin and occurred independently of T cells. NKG2D-triggered NK(More)
The selective targeting of the tumor-associated death-inducing receptors DR4 and DR5 with agonistic mAbs has demonstrated preclinical and clinical antitumor activity. However, the cellular and molecular mechanisms contributing to this efficacy remain poorly understood. In this study, using the first described C57BL/6 (B6) TRAIL-sensitive experimental tumor(More)
Adoptive cell therapy (ACT) utilizing gene-modified T cells expressing chimeric antigen receptors (CAR) has emerged as a promising regimen for the treatment of a broad range of cancers including chronic lymphoid leukaemia and neuroblastoma with recent reports of long term remission in some patients. 1,2 However, despite these encouraging outcomes, the(More)
Adoptive immunotherapy involving genetic modification of T cells with antigen-specific, chimeric, single-chain receptors is a promising approach for the treatment of cancer. To determine whether gene-modified T cells could induce antitumor effects without associated autoimmune pathology, we assessed the ability of T cells expressing an anti-Her-2 chimeric(More)