Dendritic Cell Immune Therapy to Break or Induce Tolerance

Amodio, Giada; Annoni, Andrea; Gregori, Silvia

doi:10.1007/s40778-015-0024-2

Cited by 5 publications

(6 citation statements)

References 121 publications

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“…The capacity of DCs to promote T cell activation or tolerance is the rationale for DC-based cell therapy to promote immunity for cancer and infectious diseases or tolerance in immune-mediated diseases, including in vivo gene therapy (reviewed in [112]). Our group contributed to the identification of IL-10 as key factor for promoting the differentiation of potent tolerogenic DCs.…”

Section: Immunomodulatory Approaches To Modulate Adaptive Immune Respmentioning

confidence: 99%

“…We set up a protocol to differentiate tolerogenic DCs, named DC-10, from peripheral blood monocytes cultured in the presence of GM-CSF, IL-4, and IL-10. DC-10 expressing high levels of HLA-G and IL-10 are potent inducers of allo-specific Tr1 cells [112], [113]. Thus, it can also be envisaged the application of DC-10-based cell therapy to restore tolerance to a given immunogenic transgene-derived Ag, by converting T effector cells or naïve T cells to Ag-specific Tr1 in vivo .…”

Section: Immunomodulatory Approaches To Modulate Adaptive Immune Respmentioning

confidence: 99%

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Modulation of immune responses in lentiviral vector-mediated gene transfer

Annoni

Gregori

Naldini

et al. 2019

Cellular Immunology

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Lentiviral vectors (LV) are widely used vehicles for gene transfer and therapy in pre-clinical animal models and clinical trials with promising safety and efficacy results. However, host immune responses against vector- and/or transgene-derived antigens remain a major obstacle to the success and broad applicability of gene therapy. Here we review the innate and adaptive immunological barriers to successful gene therapy, both in the context of ex vivo and in vivo LV gene therapy, mostly concerning systemic LV delivery and discuss possible means to overcome them, including vector design and production and immune modulatory strategies.

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Section: Immunomodulatory Approaches To Modulate Adaptive Immune Respmentioning

confidence: 99%

Section: Immunomodulatory Approaches To Modulate Adaptive Immune Respmentioning

confidence: 99%

Modulation of immune responses in lentiviral vector-mediated gene transfer

Annoni

Gregori

Naldini

et al. 2019

Cellular Immunology

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“…DCs play key roles in the initiation of immune responses to potent antigens (Amodio, Annoni, & Gregori, 2015). Activated DCs could present antigens to CD4 + T cells through MHC II, which subsequently stimulate B cells to generate antigen-specific antibodies (Cho, Kim, Kim, Ryu, & Woo, 2012).…”

Section: Discussionmentioning

confidence: 99%

Genetically modified rabies virus vector‐based bovine ephemeral fever virus vaccine induces protective immune responses against BEFV and RABV in mice

Zheng

Zhao

Tian

et al. 2020

Transbound Emerg Dis

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Bovine ephemeral fever (BEF) is an acute febrile infectious disease affecting mainly cattle and water buffalo. The aetiological agent of BEF is an arthropod-borne rhabdovirus, termed as bovine ephemeral fever virus (BEFV), which is endemic in tropical and subtropical regions such as Africa, Asia, Australia and the Middle East (Chaisirirat et al., 2018).BEF is also known as 3-day sickness or 3-day fever (Akakpo, 2015). The disease can result in reduction of milk production in dairy cows and loss of condition in beef cattle, causing severe economic loss (Walker & Klement, 2015). In the epidemic season, the morbidity rate may be very high (nearly 100%), but the mortality rate was usually low (<1%) (Walker & Klement, 2015). However, in recent years, the increased case of fatality (>10%) was observed in China (Zheng & Qiu, 2012) and Turkey (Tonbak et al., 2013). Moreover, the transregional incursion of BEF may occur due to the suitable insect vector migration and would lead to serious consequences (Lee, 2019). Currently, the vaccine strain used in commercially available inactivated BEFV vaccines is JB76H, a

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“…LVs are integrating vectors with intrinsic genotoxic risk. However, hematopoietic stem cell ex vivo gene therapy clinical trials conducted to correct genetic defects in primary inherited immunodeficiency (31) and in monogenic hematologic and lysosomal storage disorders (32)(33)(34) were proven effective and safe after several years of followup. Specifically, these studies did not show signs of genotoxicity in highly replicating cells, such as hematopoietic stem cells, with a pattern of integration in active genes, typical of the LV (35).…”

Section: Discussionmentioning

confidence: 99%

InsB9-23 Gene Transfer to Hepatocyte-Based Combined Therapy Abrogates Recurrence of Type 1 Diabetes After Islet Transplantation

et al. 2020

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The induction of antigen (Ag)-specific tolerance represents a therapeutic option for autoimmune diabetes. We demonstrated that administration of a lentiviral vector enabling expression of insulin B chain 9-23 (InsB9-23) (LV.InsB) in hepatocytes arrests β-cell destruction in prediabetic NOD mice by generating InsB9-23–specific FoxP3+ T regulatory cells (Tregs). LV.InsB in combination with a suboptimal dose of anti-CD3 monoclonal antibody (combined therapy [CT], 1 × 5 μg [CT5]) reverts diabetes and prevents recurrence of autoimmunity after islet transplantation in ∼50% of NOD mice. We investigated whether CT optimization could lead to abrogation of recurrence of autoimmunity. Therefore, alloislets were transplanted after optimized CT tolerogenic conditioning (1 × 25 μg [CT25]). Diabetic NOD mice conditioned with CT25 when glycemia was <500 mg/dL remained normoglycemic for 100 days after alloislet transplantation and displayed reduced insulitis, but independently from the graft. Accordingly, cured mice showed T-cell unresponsiveness to InsB9-23 stimulation and increased Treg frequency in islet infiltration and pancreatic lymph nodes. Additional studies revealed a complex mechanism of Ag-specific immune regulation driven by CT25, in which both Tregs and PDL1 costimulation cooperate to control diabetogenic cells, while transplanted islets play a crucial role, although transient, recruiting diabetogenic cells. Therefore, CT25 before alloislet transplantation represents an Ag-specific immunotherapy to resolve autoimmune diabetes in the presence of residual endogenous β-cell mass.

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Dendritic Cell Immune Therapy to Break or Induce Tolerance

Cited by 5 publications

References 121 publications

Modulation of immune responses in lentiviral vector-mediated gene transfer

Modulation of immune responses in lentiviral vector-mediated gene transfer

Genetically modified rabies virus vector‐based bovine ephemeral fever virus vaccine induces protective immune responses against BEFV and RABV in mice

InsB9-23 Gene Transfer to Hepatocyte-Based Combined Therapy Abrogates Recurrence of Type 1 Diabetes After Islet Transplantation

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