Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen

Murphy, Gerald P.; Tjoa, Benjamin A.; Ragde, Haakon; Kenny, Gerald M.; Boynton, Alton L.

doi:10.1002/(sici)1097-0045(199612)29:6<371::aid-pros5>3.0.co;2-b

Cited by 348 publications

(124 citation statements)

References 20 publications

(6 reference statements)

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“…DC have been used for prostate cancer patients with significant success, when autologous peptide-pulsed DC were administered systematically. 22 Response rate accounted for over 30%. 23 In addition, immunological monitoring documented enhanced cellular immunity in patients treated with peptide-pulsed DC.…”

Section: Discussionmentioning

confidence: 99%

TNF-α protects dendritic cells from prostate cancer-induced apoptosis

Pirtskhalaishvili

Shurin

Esche

et al. 2001

Prostate Cancer Prostatic Dis

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We have recently shown that human prostate cancer (PCa) cells induced apoptotic death of the most potent antigen-presenting cells, dendritic cells (DC), which are responsible for the induction of specific antitumor immune responses. Here we have evaluated the effect of murine PCa cells RM-1 on the survival of immature and tumor necrosis factor-a (TNF-a)-stimulated mature DC. PCa cells and DC were co-incubated for 24 -48 h and DC apoptosis was assessed by morphologic criteria, Annexin V assay, and TUNEL staining. We have shown that co-incubation of RM-1 cells with DC is accompanied by an increased level of DC apoptosis, which was mediated by decreased expression of anti-apoptotic protein Bcl-2. Stimulation of DC maturation by TNF-a resulted in increased resistance of DC to PCa-induced apoptosis. In TNF-a treated mature DC, but not in immature DC, the expression of Bcl-2 was not blocked after exposure to RM-1-derived factors. Thus, these data suggest that TNF-a-induced maturation of DC increases their resistance to PCa induced apoptosis. This is likely to be due to the stabilizing of the expression of anti-apoptotic protein Bcl-2. The difference in the sensitivity of mature and immature DC to PCa-induced cell death should be considered during the design of DC-based clinical trials for PCa patients. Prostate Cancer and Prostatic Diseases (2001) 4, 221-227.

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Section: Discussionmentioning

confidence: 99%

TNF-α protects dendritic cells from prostate cancer-induced apoptosis

Pirtskhalaishvili

Shurin

Esche

et al. 2001

Prostate Cancer Prostatic Dis

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“…Several studies have been initiated mainly employing in vitro generated DC that were loaded with specific tumor antigen peptides. 2,[8][9][10][11][12] Alternative approaches use DC that are transduced with antigen encoding cDNA or RNA (see . Such gene-modified DC offer several potential advantages over peptide loaded DC in medical therapy.…”

Section: Introductionmentioning

confidence: 99%

MHC class II presentation of endogenously expressed antigens by transfected dendritic cells

et al. 2001

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Dendritic cells (DC) present immunogenic epitopes of antigens in the context of MHC class I and class II molecules in association with costimulatory molecules, and efficiently activate both cytotoxic T cells and T helper cells. Gene modified DC expressing antigen encoding cDNA represent a particularly attractive approach for the immunotherapy of disease. We previously described a gene delivery system for DC based on receptor-mediated endocytosis of ligand/polyethylenimine (PEI) DNA transfer complexes that target cell surface receptors which are abundantly expressed on DC. Employing this gene delivery system, DC were generated that express chicken ovalbumin (OVA) cDNA as a model antigen and introduce antigen into the

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“…Such a strategy could avoid the long-term tissue culture and tedious manipulations currently needed to derive sufficient numbers of DC from each patient for therapy. 13 To maximize interaction of a tumor cell line vaccine with in situ LCs, we have transfected melanoma cell lines with a novel membranebound GM-CSF (mbGM-CSF) gene designed to enable GM-CSF expression as an integral protein on the tumor cell surface. We hypothesized that the high affinity binding of cell surface GM-CSF to its receptors on the LCs 14 in the skin would yield a strong direct interaction with the mbGM-CSF tumor cell vaccine.…”

Section: Introductionmentioning

confidence: 99%

Novel membrane-bound GM-CSF vaccines for the treatment of cancer: generation and evaluation of mbGM-CSF mouse B16F10 melanoma cell vaccine

et al. 2002

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Cancer vaccines composed of tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) are currently being clinically evaluated. To enhance the immunogenicity of GM-CSF-secreting tumor cell vaccines, a novel approach expressing GM-CSF as a membrane-bound form (mbGM-CSF) on the tumor cell surface was investigated. The intent was to enhance antigen presentation by increasing interactions between the tumor cell lines in the vaccine and GM-CSF receptor positive antigen presenting cells (APC), notably the patient's Langerhans cells residing within the intradermal injection site. B16.F10 cells engineered to express either membranebound or secreted GM-CSF were compared in the B16.F10 mouse melanoma model. We observed that mbGM-CSF on

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Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen

Cited by 348 publications

References 20 publications

TNF-α protects dendritic cells from prostate cancer-induced apoptosis

TNF-α protects dendritic cells from prostate cancer-induced apoptosis

MHC class II presentation of endogenously expressed antigens by transfected dendritic cells

Novel membrane-bound GM-CSF vaccines for the treatment of cancer: generation and evaluation of mbGM-CSF mouse B16F10 melanoma cell vaccine

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