scholarly journals IL-12p70 and IL-18 gene-modified dendritic cells loaded with tumor antigen-derived peptides or recombinant protein effectively stimulate specific Type-1 CD4+ T-cell responses from normal donors and melanoma patients in vitro

2006 ◽  
Vol 13 (8) ◽  
pp. 798-805 ◽  
Author(s):  
L Vujanovic ◽  
E Ranieri ◽  
A Gambotto ◽  
W C Olson ◽  
J M Kirkwood ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Recombinant Protein ◽  
Tumor Antigen ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Melanoma Patients

Polarized Type-1 Dendritic Cells (DC1) Producing High Levels of IL-12 Family Members Rescue Patient TH1-type Antimelanoma CD4+ T cell Responses In Vitro

2007 ◽  
Vol 30 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Amy Wesa ◽  
Pawel Kalinski ◽  
John M. Kirkwood ◽  
Tomohide Tatsumi ◽  
Walter J. Storkus
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Family Members ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses

Comparison of Antigen-Loading Strategies for DC-Based Immunotherapy of B-CLL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4821-4821
Author(s):  
Hakan Mellstedt ◽  
Parviz Kokhaei ◽  
Anders Osterborg ◽  
Aniruddha Choudhury
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Tumor Antigen ◽  
Tumor Antigens ◽  
T Cell Responses ◽  
Pcr Analysis ◽  
Apoptotic Bodies ◽  
Cell Responses

Abstract The slow indolent nature of B-CLL makes it eminently suitable for immune-based treatment strategies. Currently, there exist very few CLL-associated, defined antigen which can be used in vaccination approaches. The use of whole tumor preparations in conjunction with dendritic cells (DC) as cellular adjuvants presents an alternative method for generating therapeutic T-cell responses in CLL patients. We have examined various strategies of loading DC with whole tumor antigens; viz. tumor-DC hybrids, endocytosed apoptotic bodies, RNA or lysate from B-CLL cells. Dendritic cells were generated in vitro, using GM-CSF and IL-4 from immunomagnetically purified, CD14+ monocyte precursors obtained from the peripheral blood of B-CLL patients. The immature DC were loaded with whole tumor antigen using the above methods and matured using TNFα. The tumor antigen-loaded DC were compared for their ability to stimulate autologous T-cell responses. Among all the antigen-loading methods tested, DC that had endocytosed apoptotic bodies (Apo-DC) consistently generated the greatest numbers and magnitude of reactive T-cells as quantified in proliferation and ELISPOT assays. RT-PCR analysis for cytokine mRNA revealed that T-cells stimulated by Apo-DC resulted in an immune response that was almost entirely of the TH1 type as manifested by the production of mRNA for IFN-γ and TNFα. In contrast, other methods of loading antigen resulted in a mixed TH1-TH2 population with varying amounts of TH2 cytokines like IL-4 and IL-10. In a separate series of experiments we compared the T-cell stimulatory capacities of cryopreserved and thawed, with fresh antigen-loaded DC. The results of these studies are essential for the development of a protocol for clinical therapy of B-CLL patients using Apo-DC. Our results indicated that cryopreserved DC could be recovered with high viability. A comparison of functional abilities demonstrated that no significant differences in T-cell stimulatory capacity between cryopreserved and fresh Apo-DC could be noted over a wide variety of immunological assays. Cumulatively, our results suggest that Apo-DC may be a suitable vaccine candidate for immunotherapy of B-CLL patients.

Presentation of proteins encapsulated in sterically stabilized liposomes by dendritic cells initiates CD8+ T-cell responses in vivo

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3505-3513 ◽  
Author(s):  
Ralf Ignatius ◽  
Karsten Mahnke ◽  
Miguel Rivera ◽  
Keelung Hong ◽  
Frank Isdell ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Soluble Protein ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Sterically Stabilized Liposomes

Liposomes have been proposed as a vehicle to deliver proteins to antigen-presenting cells (APC), such as dendritic cells (DC), to stimulate strong T cell–mediated immune responses. Unfortunately, because of their instability in vivo and their rapid uptake by cells of the mononuclear phagocyte system on intravenous administration, most types of conventional liposomes lack clinical applicability. In contrast, sterically stabilized liposomes (SL) have increased in vivo stability. It is shown that both immature and mature DC take up SL into neutral or mildly acidic compartments distinct from endocytic vacuoles. These DC presented SL-encapsulated protein to both CD4+ and CD8+ T cells in vitro. Although CD4+ T-cell responses were comparable to those induced by soluble protein, CD8+ T-cell proliferation was up to 300-fold stronger when DC had been pulsed with SL-encapsulated ovalbumin. DC processed SL-encapsulated antigen through a TAP-dependent mechanism. Immunization of mice with SL-encapsulated ovalbumin led to antigen presentation by DC in vivo and stimulated greater CD8+ T-cell responses than immunization with soluble protein or with conventional or positively charged liposomes carrying ovalbumin. Therefore, the application of SL-encapsulated antigens offers a novel effective, safe vaccine approach if a combination of CD8+and CD4+ T-cell responses is desired (ie, in anti-viral or anti-tumor immunity).

Restoration of TH1 CD4+ T Cell Responses to Melanoma Antigens with Type-1 Polarized Dendritic Cells

2004 ◽  
Vol 27 (6) ◽  
pp. S34
Author(s):  
Amy Wesa ◽  
Pawel Kalinski ◽  
John M Kirkwood ◽  
Walter J Storkus
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Melanoma Antigens

Presentation of proteins encapsulated in sterically stabilized liposomes by dendritic cells initiates CD8+ T-cell responses in vivo

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3505-3513 ◽  
Author(s):  
Ralf Ignatius ◽  
Karsten Mahnke ◽  
Miguel Rivera ◽  
Keelung Hong ◽  
Frank Isdell ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Soluble Protein ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Sterically Stabilized Liposomes

Abstract Liposomes have been proposed as a vehicle to deliver proteins to antigen-presenting cells (APC), such as dendritic cells (DC), to stimulate strong T cell–mediated immune responses. Unfortunately, because of their instability in vivo and their rapid uptake by cells of the mononuclear phagocyte system on intravenous administration, most types of conventional liposomes lack clinical applicability. In contrast, sterically stabilized liposomes (SL) have increased in vivo stability. It is shown that both immature and mature DC take up SL into neutral or mildly acidic compartments distinct from endocytic vacuoles. These DC presented SL-encapsulated protein to both CD4+ and CD8+ T cells in vitro. Although CD4+ T-cell responses were comparable to those induced by soluble protein, CD8+ T-cell proliferation was up to 300-fold stronger when DC had been pulsed with SL-encapsulated ovalbumin. DC processed SL-encapsulated antigen through a TAP-dependent mechanism. Immunization of mice with SL-encapsulated ovalbumin led to antigen presentation by DC in vivo and stimulated greater CD8+ T-cell responses than immunization with soluble protein or with conventional or positively charged liposomes carrying ovalbumin. Therefore, the application of SL-encapsulated antigens offers a novel effective, safe vaccine approach if a combination of CD8+and CD4+ T-cell responses is desired (ie, in anti-viral or anti-tumor immunity).

scholarly journals Efficient In Vitro Expansion of Human Immunodeficiency Virus (HIV)-Specific T-Cell Responses by gag mRNA-Electroporated Dendritic Cells from Treated and Untreated HIV Type 1-Infected Individuals

2008 ◽  
Vol 82 (7) ◽  
pp. 3561-3573 ◽  
Author(s):  
Ellen R. Van Gulck ◽  
Guido Vanham ◽  
Leo Heyndrickx ◽  
Sandra Coppens ◽  
Katleen Vereecken ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Developing an immunotherapy to keep human immunodeficiency virus type 1 (HIV-1) replication suppressed while discontinuing highly active antiretroviral therapy (HAART) is an important challenge. In the present work, we evaluated in vitro whether dendritic cells (DC) electroporated with gag mRNA can induce HIV-specific responses in T cells from chronically infected subjects. Monocyte-derived DC, from therapy-naïve and HAART-treated HIV-1-seropositive subjects, that were electroporated with consensus codon-optimized HxB2 gag mRNA efficiently expanded T cells, secreting gamma interferon (IFN-γ) and interleukin 2 (IL-2), as well as other cytokines and perforin, upon restimulation with a pool of overlapping Gag peptides. The functional expansion levels after 1 week of stimulation were comparable in T cells from HAART-treated and treatment-naïve patients and involved both CD4+ and CD8+ T cells, with evidence of bifunctionality in T cells. Epitope mapping of p24 showed that stimulated T cells had a broadened response toward previously nondescribed epitopes. DC, from HAART-treated subjects, that were electroporated with autologous proviral gag mRNA equally efficiently expanded HIV-specific T cells. Regulatory T cells did not prevent the induction of effector T cells in this system, whereas the blocking of PD-L1 slightly increased the induction of T-cell responses. This paper shows that DC, loaded with consensus or autologous gag mRNA, expand HIV-specific T-cell responses in vitro.

scholarly journals Efficient in vitro expansion of JC virus-specific CD8+ T-cell responses by JCV peptide-stimulated dendritic cells from patients with progressive multifocal leukoencephalopathy

Virology ◽  
2009 ◽  
Vol 383 (2) ◽  
pp. 173-177 ◽  
Author(s):  
Angela Marzocchetti ◽  
Marco Lima ◽  
Troy Tompkins ◽  
Daniel.G. Kavanagh ◽  
Rajesh T. Gandhi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Jc Virus ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
In Vitro Expansion

scholarly journals Differential Effects of Viscum album Preparations on the Maturation and Activation of Human Dendritic Cells and CD4+ T Cell Responses

Molecules ◽  
2016 ◽  
Vol 21 (7) ◽  
pp. 912 ◽  
Author(s):  
Chaitrali Saha ◽  
Mrinmoy Das ◽  
Emmanuel Stephen-Victor ◽  
Alain Friboulet ◽  
Jagadeesh Bayry ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Viscum Album ◽  
Cd4 T Cell ◽  
Differential Effects ◽  
Cell Responses ◽  
Human Dendritic Cells
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