Induction of Antigen-Specific CTL by Recombinant HIV <i>Trans</i>-Activating Fusion Protein-Pulsed Human Monocyte-Derived Dendritic Cells

Tanaka, Yoshiyuki; Dowdy, Steven F.; Linehan, David C.; Eberlein, Timothy J.; Goedegebuure, Peter S.

doi:10.4049/jimmunol.170.3.1291

Cited by 33 publications

(39 citation statements)

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“…Other investigators have also reported potent immune responses using Tat-PTD as a vehicle to deliver tumor and viral antigens into dendritic cells (38). Vaccination of mice with melanoma-specific antigen-transduced monocyte-derived dendritic cells by TATmediated protein has been shown to generate durable and robust CTL responses, which regresses tumors (39).…”

Section: Discussionmentioning

confidence: 99%

“…Vaccination of mice with melanoma-specific antigen-transduced monocyte-derived dendritic cells by TATmediated protein has been shown to generate durable and robust CTL responses, which regresses tumors (39). Tanaka et al observed that a TAT fusion protein with HER-2/neu generated efficient CTL responses in contrast to the poor CTL generation observed without the presence of a TAT PTD (38). Furthermore, TAT-fusion proteins do not only induce specific CTLs but also generate potent T-helper cell responses due to simultaneous loading of the HLA class II pathway of antigen processing and presentation (40).…”

Section: Discussionmentioning

confidence: 99%

“…A nonimmunogenic 11-amino-acid motif known as the protein transduction domain (PTD: YGRK-KRRQRRR) is responsible for this phenomenon. Fusion proteins generated with this 11-amino-acid TAT (PTD) sequence traverse membrane barriers efficiently, enter the cytosol (36,37), and have immediate access to the HLA class I pathway for highly efficient antitumor CTL induction (38)(39)(40). We therefore explored NY-ESO-1 protein transduction as a safe and effective alternative to virusmediated gene delivery.…”

Section: Introductionmentioning

confidence: 99%

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Protein Transduction of Dendritic Cells for NY-ESO-1-Based Immunotherapy of Myeloma

et al. 2005

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Myeloma vaccines, based on dendritic cells pulsed with idiotype or tumor lysate, have been met with limited success, probably in part due to insufficient cross-priming of myeloma antigens. A powerful method to introduce myeloma-associated antigens into the cytosol of dendritic cells is protein transduction, a process by which proteins fused with a protein transduction domain (PTD) freely traverse membrane barriers. NY-ESO-1, an immunogenic antigen by itself highly expressed in 60% of high-risk myeloma patients, was purified to near homogeneity both alone and as a recombinant fusion protein with a PTD, derived from HIV-Tat. Efficient entry of PTD-NY-ESO-1 into dendritic cells, confirmed by microscopy, Western blotting, and intracellular flow cytometry, was achieved without affecting dendritic cell phenotype. Experiments with amiloride, which inhibits endocytosis, and N-acetyl-L-leucinyl-L-norleucinal, a proteasome inhibitor, confirmed that PTD-NY-ESO-1 entered dendritic cells by protein transduction and was degraded by the proteasome. Tetramer analysis indicated superior generation of HLA-A2.1, CD8 + T lymphocytes specific for NY-ESO-1 157-165 with PTD-NY-ESO-1 compared with NY-ESO-1 control protein (44% versus 2%, respectively). NY-ESO-1-specific T lymphocytes generated with PTD-NY-ESO-1 secreted IFN-; indicative of a Tc1-type cytokine response. Thus, PTD-NY-ESO-1 accesses the cytoplasm by protein transduction, is processed by the proteasome, and NY-ESO-1 peptides presented by HLA class I elicit NY-ESO-1-specific T lymphocytes. (Cancer Res 2005; 65(21): 10041-9)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protein Transduction of Dendritic Cells for NY-ESO-1-Based Immunotherapy of Myeloma

et al. 2005

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“…In addition to the RGD domain, Tat contains in its sequence a short and highly basic region (aa 47-59) termed "protein transduction domain" (PTD), a feature shared with very few other proteins called "penetratins" [201,202], which enables Tat-or PTDconjugated proteins to efficiently enter the cells in an energy-and receptor-independent fashion [203,204]. Thereby, the PTD peptide or the Tat protein have been largely used to deliver conjugated antigens to the MHC class I restricted-antigen presentation pathway, and to increase CTL responses to the conjugated antigen [187,[205][206][207][208][209][210]. It has also been suggested that the PTD domain itself, in addition to its antigen-delivery capability, exerts an adjuvant effect on the conjugated antigen, in a fashion similar to poly-L-arginine peptides [211], leading to increased expression of specific MHC-I/peptide complexes and activation of T cell responses [202].…”

Section: Immunomodulatory Activity Of Hiv-1 Tatmentioning

confidence: 99%

HIV-1 Tat-Based Vaccines: An Overview and Perspectives in the Field of HIV/AIDS Vaccine Development

Caputo

Gavioli

Bellino

et al. 2009

International Reviews of Immunology

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“…[4][5][6][7][8][9] PTDs can even deliver bulky molecular cargos (>100 kDa) into a wide variety of cell types. [10][11][12][13] However, to use PTDs as effective intracellular drug delivery carriers with clinical applications, it is necessary to create novel PTDs with greater protein-transduction potency than exists naturally.…”

Section: -3)mentioning

confidence: 99%

Creation of Novel Protein Transduction Domain (PTD) Mutants by a Phage Display-Based High-Throughput Screening System

Mukai

Sugita

Yamato

et al. 2006

Biological & Pharmaceutical Bulletin

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Recent advances in proteomics have allowed a number of refractory diseases, such as cancer and neurodegenerative disorders, to be studied at the molecular level. The main causative factor of such disease states is often associated with intracellular organelles or particular subcellular proteins. Thus, the intracellular organelles, proteins or genes might constitute the therapeutic target. Recently, it was discovered that certain peptides, referred to as protein transduction domains (PTDs), can penetrate cells accompanied by a large molecular cargo. Considerable research effort is currently focused on utilizing PTDs as peptide-based carriers for intracellular drug delivery. 1-3)Tat peptide, derived from the HIV-1, and Antennapedia peptide, derived from Drosophila Antennapedia homeotic transcription factor, are well known PTDs that have been tested as drug delivery carriers for various disease models. [4][5][6][7][8][9] PTDs can even deliver bulky molecular cargos (>100 kDa) into a wide variety of cell types. [10][11][12][13] However, to use PTDs as effective intracellular drug delivery carriers with clinical applications, it is necessary to create novel PTDs with greater protein-transduction potency than exists naturally.An attempt to create a novel PTD by modification of the peptide structure has already been reported. 14,15) However, because it is difficult to predict the transduction activity of the peptide based on structural information alone, novel peptides must be generated by introducing amino acid substitutions and then the effects determined by trial and error. Recently, we have successfully generated a technology for creating novel muteins (mutant proteins) that have non-native functions using a phage display system.16) This prompted us to apply phage display technology to screen for novel PTDs.The phage display system is a protein selection methodology in which a library of mutant proteins or peptides can be screened and the desired molecules easily identified by linking DNA information (genotype) with phenotype (protein expression). [16][17][18][19][20] By applying this methodology, novel PTDs can be selected such as those transduced into the cell by a different mechanism or those with tissue/cell specificity. In general, the phage display system is used to isolate antibody and peptide ligands using an affinity selection step to target the desired molecules. However, for the discovery of PTDs it is necessary to construct a screening method to select clones that are transduced into the cell rather than simply selecting those that bind to the cell surface. We designed a highthroughput screening method to isolate effective PTDs by fusing PTD with Protein Synthesis Inhibitory Factor (PSIF).21) Here, we used our methodology to identify novel Tat mutants with greater transduction potency than wild-type Tat PTD. ; 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan: and b Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University; 1-6 Yamadaoka, Suita, Osaka 565-0871, Ja...

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Induction of Antigen-Specific CTL by Recombinant HIV Trans-Activating Fusion Protein-Pulsed Human Monocyte-Derived Dendritic Cells

Cited by 33 publications

References 30 publications

Protein Transduction of Dendritic Cells for NY-ESO-1-Based Immunotherapy of Myeloma

Protein Transduction of Dendritic Cells for NY-ESO-1-Based Immunotherapy of Myeloma

HIV-1 Tat-Based Vaccines: An Overview and Perspectives in the Field of HIV/AIDS Vaccine Development

Creation of Novel Protein Transduction Domain (PTD) Mutants by a Phage Display-Based High-Throughput Screening System

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