Green fluorescent protein expression in dendritic cells enhances their immunogenicity and elicits specific cytotoxic T-cell responses in humans

Re, Francesca; Srinivasan, Ramaprasad; Igarashi, Takehito; Marincola, Franco; Childs, Richard W.

doi:10.1016/j.exphem.2003.10.014

Cited by 32 publications

(29 citation statements)

References 16 publications

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“…Another study showed that GFP, delivered into dendritic cells (DCs) by an adenoviral vector or following protein pulsing, could significantly modify DC phenotype, into a terminal maturation-like process which enhanced their immunostimulatory capacity (Re et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy

2006

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The ideal cancer treatment should both destroy the primary tumour and at the same time educate the immune system to recognise the tumour as foreign so that distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the i.v. administration of photosensitisers followed by illumination of the tumour with red light producing reactive oxygen species that eventually cause vascular shutdown and tumour cell death by apoptosis and necrosis. Anti-tumour immunity is stimulated after PDT due to the acute inflammatory response, generation of tumour-specific antigens, and induction of heat-shock proteins. Green fluorescent protein (GFP) is used as an optical reporter to noninvasively image the progression of mouse tumours, and in addition, may act as a foreign (jellyfish) antigen. We asked whether GFP-expressing tumours could be used to monitor the response of tumour-bearing mice to PDT, and whether the tumour response differed when a nonimmunogenic tumour cell line was transduced with GFP. We injected RIF-1 or RIF-1 EGFP (stably transduced with a retroviral vector) cells in the leg of C3H/HeN mice and both the cells and tumour grew equally well. We used PDT with benzoporphyrin derivative and a short drug-light interval. There were complete cures and 100% mouse survival of RIF-1 EGFP while RIF-1 wild-type tumours all recurred. Cured mice were resistant to rechallenge with RIF-1 EGFP cells and a rechallenge with wild-type RIF-1 cells grew significantly slower. There was also slower RIF-1 EGFP rechallenge growth but no rejection when RIF-1 EGFP tumours were surgically removed. There was a low rate of PDT cure of tumours when RIF-1 cells were transduced with an empty retroviral vector. The presence of antibodies against EGFP in mouse serum suggests EGFP can act as a foreign antigen and PDT can then stimulate a long-term memory immune response.

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Section: Discussionmentioning

confidence: 99%

A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy

2006

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“…Supporting our data, previously it has been shown that peptides derived from eGFP degradation are immunogenic in rodents, non-human primates, and humans. [26][27][28][29][30] As a consequence, survival of eGFP gene-modified cells was reduced or completely abrogated in transplanted animals. [27][28][29][30] Furthermore, similar to our findings, other reports suggest that immunostimulatory properties of DCs are linked to their maturation state.…”

Section: Immune Responses To Gene-modified Dendritic Cells N Chinnasamentioning

confidence: 99%

“…We transduced them with a HIV-1-based self-inactivating (SIN) lentiviral vector expressing a widely used reporter molecule, the enhanced green fluorescent protein (eGFP). Previously, it has been shown that eGFP is immunogenic in human, 26 non-human primates 27,28 and in murine models. 29,30 Evidences also suggest immune rejection of transplanted eGFP-positive cells in non-human primate recipients in myeloablative 27 as well as nonablative settings.…”

Section: Introductionmentioning

confidence: 99%

Ex vivo generation of genetically modified dendritic cells for immunotherapy: implications of lymphocyte contamination

et al. 2005

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Genetically modified dendritic cell (DC) vaccines expressing tumor-associated antigens are currently used for cancer immunotherapy. Peripheral blood (PB) monocyte precursors are a relatively convenient source of DCs for use in clinical studies, but are often contaminated by lymphocytes. The current study was conducted to examine the impact of Tlymphocyte contamination on genetically modified DC product. PB monocyte-derived DCs were efficiently transduced (75-95%) with an HIV-1-based self-inactivating lentiviral vector encoding a model antigen, the enhanced green fluorescent protein (eGFP). The lymphocyte-free DC culture transduced with Lenti-eGFP showed stable expression of eGFP without measurable decline in viability. In contrast, the eGFP-positive DCs disappeared rapidly in transduced DC cultures containing lymphocyte contaminants, concurrent with detectable activation and expansion of T-lymphocytes. Upon antigen recall, these T cells elicited major histocompatability complex-restricted antigen-specific cytotoxicity against eGFP-positive autologous DCs and mitogen-stimulated T lymphoblasts, mainly through the perforin-mediated pathway. In summary, this study demonstrate that the relative purity of DC cultures could determine the persistence of gene-modified DC, which may affect the induction of effective immune responses by DC vaccination strategies. Gene Therapy (2005) 12, 259-271.

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“…Fluorescent and bioluminescent imaging offer a relatively costeffective way to study liver metastases but suffer from poor resolution and the requirement to transfect endogenous reporter genes into the cell line of interest (1,2). The expression of foreign reporter proteins may lead to increased immunogenicity and thus must be carefully examined for their effect on the metastatic model being studied (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional High-Frequency Ultrasound Imaging for Longitudinal Evaluation of Liver Metastases in Preclinical Models

et al. 2005

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Liver metastasis is a clinically significant contributor to the mortality associated with melanoma, colon, and breast cancer. Preclinical mouse models are essential to the study of liver metastasis, yet their utility has been limited by the inability to study this dynamic process in a noninvasive and longitudinal manner. This study shows that three-dimensional high-frequency ultrasound can be used to noninvasively track the growth of liver metastases and evaluate potential chemotherapeutics in experimental liver metastasis models. Liver metastases produced by mesenteric vein injection of B16F1 (murine melanoma), PAP2 (murine H-ras-transformed fibroblast), HT-29 (human colon carcinoma), and MDA-MB-435/HAL (human breast carcinoma) cells were identified and tracked longitudinally. Tumor size and location were verified by histologic evaluation. Tumor volumes were calculated from the three-dimensional volumetric data, with individual liver metastases showing exponential growth. The importance of volumetric imaging to reduce uncertainty in tumor volume measurement was shown by comparing threedimensional segmented volumes with volumes estimated from diameter measurements and the assumption of an ellipsoid shape. The utility of high-frequency ultrasound imaging in the evaluation of therapeutic interventions was established with a doxorubicin treatment trial. These results show that three-dimensional high-frequency ultrasound imaging may be particularly well suited for the quantitative assessment of metastatic progression and the evaluation of chemotherapeutics in preclinical liver metastasis models.

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Green fluorescent protein expression in dendritic cells enhances their immunogenicity and elicits specific cytotoxic T-cell responses in humans

Cited by 32 publications

References 16 publications

A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy

A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy

Ex vivo generation of genetically modified dendritic cells for immunotherapy: implications of lymphocyte contamination

Three-dimensional High-Frequency Ultrasound Imaging for Longitudinal Evaluation of Liver Metastases in Preclinical Models

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