Transduction of dendritic cells by antigen-encoding lentiviral vectors permits antigen processing and MHC class I–dependent presentation

Zarei, Shohreh; Leuba, Florence; Arrighi, Jean‐François; Hauser, Conrad; Piguet, Vincent

doi:10.1067/mai.2002.124663

Cited by 33 publications

(27 citation statements)

References 31 publications

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“…Reported efficiencies of human DC transduction have varied considerably from 30-40% in some studies 48,49 , to as much as 70-100% in others 20,[50][51][52] . Similar efficiencies were observed in the transduction of murine DCs, by lentivectors with transduction efficiencies reported from 40-50% to more than 90% 16,19,50,53 . The observed capacity of lentivectors to transduce non-dividing cells suggests that either mature or immature human DCs can be transduced by lentivector.…”

Section: Transduction Of Apcs With Recombinant Lentivectorsupporting

confidence: 58%

Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

Munn

Falo

2007

Expert Review of Vaccines

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SummaryEncouraged by remarkable successes in preventing infectious diseases and by the well established potential of immune system for controlling tumor growth, active therapeutic immunization approaches hold great promise for treating malignant tumors. In recent years, engineered recombinant viral vectors have been carefully examined as genetic immunization vehicles and have been demonstrated to induce potent T cell mediated immune responses that can control tumor growth. Very recent efforts suggest that lentivectors possess important advantages over other candidate recombinant viral vectors for genetic immunization. Here we review the development of recombinant lentivectors and the characteristics of T cell immune responses elicited by lentivector immunization, including the mechanism of T cell priming with a focus on the role of skin dendritic cells (DC) and potential applications for tumor immunotherapy.

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Section: Transduction Of Apcs With Recombinant Lentivectorsupporting

confidence: 58%

Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

Munn

Falo

2007

Expert Review of Vaccines

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“…In those reports, it was shown that lentiviral transduction did not hamper the subsequent maturation of these DC with strong stimuli, such as inflammatory cytokines, LPS, or CpG oligonucleotides (7,14,34,48). Only He et al investigated whether the lentiviral transduction of DC in itself resulted in DC activation (20).…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Lentiviral Vector Immunogenicity Is Mediated by Toll-Like Receptor 3 (TLR3) and TLR7

Breckpot

Escors

Arce

et al. 2010

J Virol

125

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Lentiviral vectors are promising vaccine vector candidates that have been tested extensively in preclinical models of infectious disease and cancer immunotherapy. They are also used in gene therapy clinical trials both for the ex vivo modification of cells and for direct in vivo injection. It is therefore critical to understand the mechanism(s) by which such vectors might stimulate the immune system. We evaluated the effect of lentiviral vectors on myeloid dendritic cells (DC), the main target of lentiviral transduction following subcutaneous immunization. The activation of DC cultures was independent of the lentiviral pseudotype but dependent on cell entry and reverse transcription. In vivo-transduced DC also displayed a mature phenotype, produced tumor necrosis factor alpha (TNF-␣), and stimulated naive CD8 ؉ T cells. The lentiviral activation of DC was Toll-like receptor (TLR) dependent, as it was inhibited in TRIF/MyD88 knockout (TRIF/MyD88؊/؊ ) DC. TLR3 ؊/؊ or TLR7 ؊/؊ DC were less activated, and reverse transcription was important for the activation of TLR7 ؊/؊ DC. Moreover, lentivirally transduced DC lacking TLR3 or TLR7 had an impaired capacity to induce antigenspecific CD8؉ T-cell responses. In conclusion, we demonstrated TLR-dependent DC activation by lentiviral vectors, explaining their immunogenicity. These data allow the rational development of strategies to manipulate the host's immune response to the transgene.

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“…Importantly, like oncoretroviral vectors, lvv do not encode viral proteins, thereby minimizing the potential for interfering with the function of transduced DCs (39). Recently, third-generation lvv with enhanced safety profiles have been developed and used to efficiently transduce murine DCs and human DCs (36,37,40). These improved vectors contain a chimeric Rous sarcoma virus (RSV)/HIV 5Ј long terminal repeat (5ЈLTR) enhancer and promoter to initiate the transcription of genomic viral RNA (41).…”

Section: Endritic Cells (Dcs)mentioning

confidence: 99%

Immunization with Lentiviral Vector-Transduced Dendritic Cells Induces Strong and Long-Lasting T Cell Responses and Therapeutic Immunity

He¹,

Zhang²,

Zhang

et al. 2005

The Journal of Immunology

142

152

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Dendritic cell (DC) therapies are currently being evaluated for the treatment of cancer. The majority of ongoing clinical trials use DCs loaded with defined antigenic peptides or proteins, or tumor-derived products, such as lysates or apoptotic cells, as sources of Ag. Although several theoretical considerations suggest that DCs expressing transgenic protein Ags may be more effective immunogens than protein-loaded cells, methods for efficiently transfecting DCs are only now being developed. In this study we directly compare the immunogenicity of peptide/protein-pulsed DCs with lentiviral vector-transduced DCs, and their comparative efficacy in tumor immunotherapy. Maturing, bone marrow-derived DCs can be efficiently transduced with lentiviral vectors, and transduction does not affect DC maturation, plasticity, or Ag presentation function. Transduced DCs efficiently process and present both MHC class I- and II-restricted epitopes from the expressed transgenic Ag OVA. Compared with peptide- or protein-pulsed DCs, lentiviral vector-transduced DCs elicit stronger and longer-lasting T cell responses in vivo, as measured by both in vivo killing assays and intracellular production of IFN-γ by Ag-specific T cells. In the B16-OVA tumor therapy model, the growth of established tumors was significantly inhibited by a single immunization using lentiviral vector-transduced DCs, resulting in significantly longer survival of immunized animals. These results suggest that compared with Ag-pulsed DCs, vaccination with lentiviral vector-transduced DCs may achieve more potent antitumor immunity. These data support the further development of lentiviral vectors to transduce DCs with genes encoding Ags or immunomodulatory adjuvants to generate and control systemic immune responses.

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Transduction of dendritic cells by antigen-encoding lentiviral vectors permits antigen processing and MHC class I–dependent presentation

Cited by 33 publications

References 31 publications

Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

HIV-1 Lentiviral Vector Immunogenicity Is Mediated by Toll-Like Receptor 3 (TLR3) and TLR7

Immunization with Lentiviral Vector-Transduced Dendritic Cells Induces Strong and Long-Lasting T Cell Responses and Therapeutic Immunity

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