Side-by-Side Comparison of Lentivirally Transduced and mRNA-Electroporated Dendritic Cells: Implications for Cancer Immunotherapy Protocols

Dullaers, Mélissa; Breckpot, Karine; Meirvenne, Sonja Van; Bonehill, Aude; Tuyaerts, Sandra; Michiels, Annelies; Straetman, Lieven; Heirman, Carlo; Greef, Catherine De; Bruggen, Pierre van der; Thielemans, Kris

doi:10.1016/j.ymthe.2004.07.017

Cited by 79 publications

(68 citation statements)

References 50 publications

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“…We have investigated the duration of Ag presentation in vivo and found that Ag presentation could be measured for up to two weeks after transfer of lentivector transfected DCs 16 . This is consistent with reports that Ag expression can last at least 7 days in DCs after ex vivo transduction with lentivector 78 . Our studies demonstrate that the duration of in vivo Ag presentation is even longer following direct skin immunization with lentivector.…”

Section: Prolongedsupporting

confidence: 93%

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: Prolongedsupporting

confidence: 93%

Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

Munn

Falo

2007

Expert Review of Vaccines

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“…Nonviral transfection of DCs would obviate this obstacle, and the delivery of Ag-encoding mRNA to DCs has been shown to result in Ag expression and stimulation of Ag-specific T cell responses (61,62). However, in a direct comparison, mRNA-transfected DCs were less immunogenic in vivo than lvv-transduced DCs (63). Interestingly, although introduction of mRNA into DCs by electroporation resulted in efficient transgene expression, electroporated DCs showed a 10-fold reduction in IL-12p70 secretion compared with unmodified or lentivirally transduced DCs (63).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, although introduction of mRNA into DCs by electroporation resulted in efficient transgene expression, electroporated DCs showed a 10-fold reduction in IL-12p70 secretion compared with unmodified or lentivirally transduced DCs (63). Overcoming this defect by retrovirus-mediated cotransfection of IL-12p70 overcame this limitation, but added an additional level of complexity (63).…”

Section: Discussionmentioning

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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“…100 No pseudotransduction with nonviral eGFP delivered by tNGFRencoding lentiviruses was observed. 101 Importantly, the variability in transduction efficiency among different reports reflects the diversity in DC sources, techniques and vectors used for transduction.…”

Section: Lentiviral Transduction Of Dcsmentioning

confidence: 99%

Lentiviral vectors for cancer immunotherapy: transforming infectious particles into therapeutics

2007

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Lentiviral vectors have emerged as promising tools for both gene therapy and immunotherapy purposes. They exhibit several advantages over other viral systems in that they are less immunogenic and are capable of transducing a wide range of different cell types, including dendritic cells (DC). DC transduced ex vivo with a whole range of different (tumor) antigens were capable of inducing strong antigen-specific T-cell responses, both in vitro and in vivo. Recently, the administration of lentiviral vectors in vivo has gained substantial interest as an alternative method for antigenspecific immunization. This method offers a number of advantages over DC vaccines as the same lentivirus can in principle be used for all patients resulting in a significantly reduced cost and requirement for considerably less expertise for the generation and administration of lentiviral vaccines. By selectively targeting lentiviral vectors to, or restricting transgene expression in certain cell types, selectivity, safety and efficacy can be further improved. This review will focus on the use of direct administration of lentiviral vectors encoding tumor-associated antigens (TAA) for the induction of tumor-specific immune responses in vivo, with a special focus on problems related to the generation of large amounts of highly purified virus and specific targeting of antigenpresenting cells (APC).

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Side-by-Side Comparison of Lentivirally Transduced and mRNA-Electroporated Dendritic Cells: Implications for Cancer Immunotherapy Protocols

Cited by 79 publications

References 50 publications

Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

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

Lentiviral vectors for cancer immunotherapy: transforming infectious particles into therapeutics

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