Generating a T cell tumor-specific immune response in vivo: can flt3-ligand-generated dendritic cells tip the balance?

1999 ◽  
Vol 48 (6) ◽  
pp. 281-286 ◽  
Author(s):  
H. J. McKenna
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
T Cell ◽  
Cell Tumor ◽  
Specific Immune Response ◽  
Flt3 Ligand ◽  
Tumor Specific Immune Response

scholarly journals Bridging channel dendritic cells induce immunity to transfused red blood cells

2016 ◽  
Vol 213 (6) ◽  
pp. 887-896 ◽  
Author(s):  
Samuele Calabro ◽  
Antonia Gallman ◽  
Uthaman Gowthaman ◽  
Dong Liu ◽  
Pei Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Major Complication ◽  
Life Saving ◽  
T Cell Help ◽  
Rbc Transfusion

Red blood cell (RBC) transfusion is a life-saving therapeutic tool. However, a major complication in transfusion recipients is the generation of antibodies against non-ABO alloantigens on donor RBCs, potentially resulting in hemolysis and renal failure. Long-lived antibody responses typically require CD4+ T cell help and, in murine transfusion models, alloimmunization requires a spleen. Yet, it is not known how RBC-derived antigens are presented to naive T cells in the spleen. We sought to answer whether splenic dendritic cells (DCs) were essential for T cell priming to RBC alloantigens. Transient deletion of conventional DCs at the time of transfusion or splenic DC preactivation before RBC transfusion abrogated T and B cell responses to allogeneic RBCs, even though transfused RBCs persisted in the circulation for weeks. Although all splenic DCs phagocytosed RBCs and activated RBC-specific CD4+ T cells in vitro, only bridging channel 33D1+ DCs were required for alloimmunization in vivo. In contrast, deletion of XCR1+CD8+ DCs did not alter the immune response to RBCs. Our work suggests that blocking the function of one DC subset during a narrow window of time during RBC transfusion could potentially prevent the detrimental immune response that occurs in patients who require lifelong RBC transfusion support.

Simultaneous in vivo tracking of dendritic cells and priming of an antigen-specific immune response

Biomaterials ◽  
2011 ◽  
Vol 32 (26) ◽  
pp. 6254-6263 ◽  
Author(s):  
Young-Woock Noh ◽  
Yong-Suk Jang ◽  
Kook-Jin Ahn ◽  
Yong Taik Lim ◽  
Bong Hyun Chung
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Specific Immune Response

scholarly journals Exosomes Isolated from Ascites of T-Cell Lymphoma-Bearing Mice Expressing Surface CD24 and HSP-90 Induce a Tumor-Specific Immune Response

2017 ◽  
Vol 8 ◽  
Author(s):  
Florencia Menay ◽  
Leticia Herschlik ◽  
Julieta De Toro ◽  
Federico Cocozza ◽  
Rodrigo Tsacalian ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Specific Immune Response ◽  
Hsp 90 ◽  
Tumor Specific Immune Response

Flt3 ligand enhances thymic-dependent and thymic-independent immune reconstitution

Blood ◽  
2004 ◽  
Vol 104 (9) ◽  
pp. 2794-2800 ◽  
Author(s):  
Terry J. Fry ◽  
Manoj Sinha ◽  
Matthew Milliron ◽  
Yu-Waye Chu ◽  
Veena Kapoor ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Reconstitution ◽  
Cell Receptor ◽  
Cell Depletion ◽  
Athymic Mice ◽  
Flt3 Ligand ◽  
T Cell Depletion

Abstract Despite recent progress in our understanding of the biology of T-cell homeostasis, clinically available therapies to substantially improve immune reconstitution in patients sustaining T-cell depletion are lacking. T cells are regenerated via a dynamic interplay between thymopoiesis and thymic-independent homeostatic peripheral expansion (HPE). Using athymic mice subjected to T-cell depletion, we observed that HPE is critically dependent on dendritic cells (DCs) for presentation of antigen, raising the possibility that the availability of DCs might be limiting in vivo for HPE to occur efficiently. Indeed, flt3 ligand (flt3L) treatment of athymic mice subjected to T-cell depletion (without DC depletion) substantially enhanced HPE and improved immune competence. Following bone marrow transplantation (BMT) in athymic hosts, both dendritic cells and T cells were profoundly depleted and flt3L therapy restored DC numbers and enhanced HPE. In addition, thymus-bearing BMT recipients treated with flt3L regenerated increased numbers of thymic-dependent progeny with increased numbers of T-cell receptor excision circle (TREC)-positive T cells, indicating increased thymopoiesis. Therefore, flt3L is a potent immunorestorative agent that enhances both thymic-dependent and thymic-independent pathways of T-cell regeneration. (Blood. 2004;104:2794-2800)

scholarly journals Inhibition of Phosphatidylserine Recognition Heightens the Immunogenicity of Irradiated Lymphoma Cells In Vivo

2004 ◽  
Vol 200 (9) ◽  
pp. 1157-1165 ◽  
Author(s):  
Attilio Bondanza ◽  
Valérie S. Zimmermann ◽  
Patrizia Rovere-Querini ◽  
Javier Turnay ◽  
Ingrid E. Dumitriu ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Tumor Cells ◽  
Proinflammatory Cytokines ◽  
Annexin V ◽  
Immune Rejection ◽  
Lymphoma Cells ◽  
High Affinity ◽  
Tumor Specific Immune Response

Strategies to enhance the immunogenicity of tumors are urgently needed. Although vaccination with irradiated dying lymphoma cells recruits a tumor-specific immune response, its efficiency as immunogen is poor. Annexin V (AxV) binds with high affinity to phosphatidylserine on the surface of apoptotic and necrotic cells and thereby impairs their uptake by macrophages. Here, we report that AxV preferentially targets irradiated lymphoma cells to CD8+ dendritic cells for in vivo clearance, elicits the release of proinflammatory cytokines and dramatically enhances the protection elicited against the tumor. The response was endowed with both memory, because protected animals rejected living lymphoma cells after 72 d, and specificity, because vaccinated animals failed to reject unrelated neoplasms. Finally, AxV–coupled irradiated cells induced the regression of growing tumors. These data indicate that endogenous adjuvants that bind to dying tumor cells can be exploited to target tumors for immune rejection.

scholarly journals 771 Novel lipid nanoparticle vaccine platform for efficient delivery of high- and low-affinity epitopes

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A806-A806
Author(s):  
Unnur Jóna Björgvinsdóttir ◽  
Laura Stentoft Carstensen ◽  
Anna Colliander ◽  
Ditte Elisabeth Jæhger ◽  
Gael Clergeaud Veiga ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
Vaccine Platform ◽  
Particle Uptake ◽  
High Affinity ◽  
Lipid Nanoparticle

BackgroundTherapeutic cancer vaccines represent an intriguing approach to cancer immunotherapy and they have been widely explored for the last decade. As opposed to standard modalities, such as surgery and chemotherapy, an effective vaccine-based immune response may provide protection against metastatic disease. Peptide based vaccines can elicit a highly targeted immune response and include a simple, fast and cost-effective production due to recent developments in solid phase peptide synthesis. Recent development within the field of COVID-19 vaccines has highlighted the use of lipid nanoparticles as an effective drug delivery system for vaccination. Incorporation of peptide antigens into engineered micro- and nanoparticles enables induction of a potent T cell response, partly attributed to prolonged and improved antigen presentation by dendritic cells after particle internalization. Peptide-based vaccines are often based on delivery of high-affinity T cell model epitopes. However, the therapeutic relevance of vaccination with low-affinity epitopes is gaining increasing support following the observation that high-affinity epitopes can promote T cell exhaustion resulting from excessive T cell receptor stimulation. Here, we characterize and evaluate a novel lipid nanoparticle (LNP) vaccine platform that is suited for delivery of both high- and low-affinity epitopes in the setting of therapeutic cancer vaccination.MethodsLNPs were formulated to carry high- or low-affinity peptide epitopes from Ovalbumin (OVA) in conjunction with the TLR7 agonist 1V270. The peptides were anchored to the surface of the LNPs via a reducible DSPE-PEG2000 linker system. The therapeutic vaccine platform was evaluated in vivo both as a monotherapy and in combination with adoptive transfer of OT-I T cells in the syngeneic B16-OVA murine melanoma model.ResultsThe LNP vaccine promotes efficient antigen-release and ensures high, continuous antigen-presentation by antigen-presenting cells. While the LNPs can be administered via multiple routes, intratumoral vaccination favors enhanced particle uptake in dendritic cells in the tumor. Formulated with either high- or low-affinity epitopes, intratumorally delivered vaccine particles promote superior tumor-infiltration of adoptively transferred T cells, which translates into potent anti-tumor efficacy in vivo. Finally, we show that vaccination with both CD8+ and CD4+ epitopes can delay tumor growth and prolong survival in an antigen-dependent manner.ConclusionsThis study presents a versatile and multi-purpose LNP vaccine platform that ensures effective delivery of high- and low-affinity epitopes. Intratumoral administration promotes vaccine particle uptake by intratumoral dendritic cells, which is followed by T cell infiltration and anti-tumor efficacy in vivo.Ethics ApprovalAll animal procedures were approved by the Danish National Animal Experiments Inspectorate.

scholarly journals Polyomavirus-Infected Dendritic Cells Induce Antiviral CD8+ T Lymphocytes

2000 ◽  
Vol 74 (9) ◽  
pp. 4093-4101 ◽  
Author(s):  
Donald R. Drake ◽  
Janice M. Moser ◽  
Annette Hadley ◽  
John D. Altman ◽  
Charles Maliszewski ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Acute Infection ◽  
Flt3 Ligand ◽  
Cell Responses ◽  
Viral Epitope ◽  
Induced Tumors ◽  
Antigen Presenting

ABSTRACT CD8+ T cells are critical for the clearance of acute polyomavirus infection and the prevention of polyomavirus-induced tumors, but the antigen-presenting cell(s) involved in generating polyomavirus-specific CD8+ T cells have not been defined. We investigated whether dendritic cells and macrophages are permissive for polyomavirus infection and examined their potential for inducing antiviral CD8+ T cells. Although dendritic cells and macrophages both supported productive polyomavirus infection, dendritic cells were markedly more efficient at presenting the immunodominant viral epitope to CD8+ T cells. Additionally, infected dendritic cells, but not infected macrophages, primed anti-polyomavirus CD8+ T cells in vivo. Treatment with Flt3 ligand, a hematopoietic growth factor that dramatically expands the number of dendritic cells, markedly enhanced the magnitude of virus-specific CD8+ T-cell responses during acute infection and the pool of memory anti-polyomavirus CD8+ T cells. These findings suggest that virus-infected dendritic cells induce polyomavirus-specific CD8+ T cells in vivo and raise the potential for their use as cellular adjuvants to promote CD8+ T cell surveillance against polyomavirus-induced tumors.

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