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Abstract
To increase the safety and possibly efficacy of HIV-1 derived lentivectors (LVs) as an anti-cancer vaccine, we recently developed the Nanobody (Nb) display technology to target LVs to antigen presenting cells (APCs). In this study, we extend these data with exclusive targeting of LVs to conventional dendritic cells (DCs), which are believed to be the main cross-presenting APCs for the induction of a TH1-conducted antitumor immune response. The immunogenicity of these DC-subtype targeted LVs was compared to that of broad tropism, general APC-targeted and non-infectious LVs. Intranodal immunization with ovalbumin encoding LVs induced proliferation of antigen specific CD4(+) T cells, irrespective of the LVs' targeting ability. However, the cytokine secretion profile of the restimulated CD4(+) T cells demonstrated that general APC targeting induced a similar TH1-profile as the broad tropism LVs while transduction of conventional DCs alone induced a similar and less potent TH1 profile as the non-infectious LVs. This observation contradicts the hypothesis that conventional DCs are the most important APCs and suggests that the activation of other APCs is also meaningful. Despite these differences, all targeted LVs were able to stimulate cytotoxic T lymphocytes, be it to a lesser extent than broad tropism LVs. Furthermore this induction was shown to be dependent on type I interferon for the targeted and non-infectious LVs, but not for broad tropism LVs. Finally we demonstrated that the APC-targeted LVs were as potent in therapy as broad tropism LVs and as such deliver on their promise as safer and efficacious LV-based vaccines.
Keywords
IN-VIVO, CANCER-IMMUNOTHERAPY, LENTIVIRAL VECTORS, ANTIGEN-PRESENTING CELLS, CD8-ALPHA(+) DENDRITIC CELLS, T-CELL RESPONSES, antitumor immunotherapy, vaccine, antigen presenting cell, lentivector, targeting, MESSENGER-RNA, VIRAL VECTORS, TUMOR-ANTIGEN, GENE-TRANSFER

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Citation

Please use this url to cite or link to this publication:

MLA
Goyvaerts, Cleo et al. “Immunogenicity of Targeted Lentivectors.” ONCOTARGET 5.3 (2014): 704–715. Print.
APA
Goyvaerts, C., De Groeve, K., Van Lint, S., Heirman, C., Vanginderachter, J. A., De Baetselier, P., Raes, G., et al. (2014). Immunogenicity of targeted lentivectors. ONCOTARGET, 5(3), 704–715.
Chicago author-date
Goyvaerts, Cleo, Kurt De Groeve, Sandra Van Lint, Carlo Heirman, Jo A Vanginderachter, Patrick De Baetselier, Geert Raes, Kris Thielemans, and Karine Breckpot. 2014. “Immunogenicity of Targeted Lentivectors.” Oncotarget 5 (3): 704–715.
Chicago author-date (all authors)
Goyvaerts, Cleo, Kurt De Groeve, Sandra Van Lint, Carlo Heirman, Jo A Vanginderachter, Patrick De Baetselier, Geert Raes, Kris Thielemans, and Karine Breckpot. 2014. “Immunogenicity of Targeted Lentivectors.” Oncotarget 5 (3): 704–715.
Vancouver
1.
Goyvaerts C, De Groeve K, Van Lint S, Heirman C, Vanginderachter JA, De Baetselier P, et al. Immunogenicity of targeted lentivectors. ONCOTARGET. 2014;5(3):704–15.
IEEE
[1]
C. Goyvaerts et al., “Immunogenicity of targeted lentivectors,” ONCOTARGET, vol. 5, no. 3, pp. 704–715, 2014.
@article{6963187,
  abstract     = {To increase the safety and possibly efficacy of HIV-1 derived lentivectors (LVs) as an anti-cancer vaccine, we recently developed the Nanobody (Nb) display technology to target LVs to antigen presenting cells (APCs). In this study, we extend these data with exclusive targeting of LVs to conventional dendritic cells (DCs), which are believed to be the main cross-presenting APCs for the induction of a TH1-conducted antitumor immune response. The immunogenicity of these DC-subtype targeted LVs was compared to that of broad tropism, general APC-targeted and non-infectious LVs. Intranodal immunization with ovalbumin encoding LVs induced proliferation of antigen specific CD4(+) T cells, irrespective of the LVs' targeting ability. However, the cytokine secretion profile of the restimulated CD4(+) T cells demonstrated that general APC targeting induced a similar TH1-profile as the broad tropism LVs while transduction of conventional DCs alone induced a similar and less potent TH1 profile as the non-infectious LVs. This observation contradicts the hypothesis that conventional DCs are the most important APCs and suggests that the activation of other APCs is also meaningful. Despite these differences, all targeted LVs were able to stimulate cytotoxic T lymphocytes, be it to a lesser extent than broad tropism LVs. Furthermore this induction was shown to be dependent on type I interferon for the targeted and non-infectious LVs, but not for broad tropism LVs. Finally we demonstrated that the APC-targeted LVs were as potent in therapy as broad tropism LVs and as such deliver on their promise as safer and efficacious LV-based vaccines.},
  author       = {Goyvaerts, Cleo and De Groeve, Kurt and Van Lint, Sandra and Heirman, Carlo and Vanginderachter, Jo A and De Baetselier, Patrick and Raes, Geert and Thielemans, Kris and Breckpot, Karine},
  issn         = {1949-2553},
  journal      = {ONCOTARGET},
  keywords     = {IN-VIVO,CANCER-IMMUNOTHERAPY,LENTIVIRAL VECTORS,ANTIGEN-PRESENTING CELLS,CD8-ALPHA(+) DENDRITIC CELLS,T-CELL RESPONSES,antitumor immunotherapy,vaccine,antigen presenting cell,lentivector,targeting,MESSENGER-RNA,VIRAL VECTORS,TUMOR-ANTIGEN,GENE-TRANSFER},
  language     = {eng},
  number       = {3},
  pages        = {704--715},
  title        = {Immunogenicity of targeted lentivectors},
  url          = {http://dx.doi.org/10.18632/oncotarget.1680},
  volume       = {5},
  year         = {2014},
}

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