دورية أكاديمية

Immunogenicity of targeted lentivectors

التفاصيل البيبلوغرافية
العنوان: Immunogenicity of targeted lentivectors
المؤلفون: Goyvaerts, Cleo, De Groeve, Kurt, Van Lint, Sandra, Heirman, Carlo, Vanginderachter, Jo A, De Baetselier, Patrick, Raes, Geert, Thielemans, Kris, Breckpot, Karine
المصدر: ONCOTARGET ; ISSN: 1949-2553
سنة النشر: 2014
المجموعة: Ghent University Academic Bibliography
مصطلحات موضوعية: Biology and Life Sciences, 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
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
العلاقة: https://biblio.ugent.be/publication/6963187Test; http://hdl.handle.net/1854/LU-6963187Test; http://dx.doi.org/10.18632/oncotarget.1680Test; https://biblio.ugent.be/publication/6963187/file/6963778Test
DOI: 10.18632/oncotarget.1680
الإتاحة: https://doi.org/10.18632/oncotarget.1680Test
https://biblio.ugent.be/publication/6963187Test
http://hdl.handle.net/1854/LU-6963187Test
https://biblio.ugent.be/publication/6963187/file/6963778Test
حقوق: No license (in copyright) ; info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.DE331B00
قاعدة البيانات: BASE