| Autor: |
Odegard JM; Immune Design Corp. †TRIA Bioscience Corp., Seattle, WA., Kelley-Clarke B, Tareen SU, Campbell DJ, Flynn PA, Nicolai CJ, Slough MM, Vin CD, McGowan PJ, Nelson LT, Ter Meulen J, Dubensky TW Jr, Robbins SH |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of immunotherapy (Hagerstown, Md. : 1997) [J Immunother] 2015 Feb-Mar; Vol. 38 (2), pp. 41-53. |
| DOI: |
10.1097/CJI.0000000000000067 |
| Abstrakt: |
Dendritic cells (DCs) are essential antigen-presenting cells for the initiation of cytotoxic T-cell responses and therefore attractive targets for cancer immunotherapy. We have developed an integration-deficient lentiviral vector termed ID-VP02 that is designed to deliver antigen-encoding nucleic acids selectively to human DCs in vivo. ID-VP02 utilizes a genetically and glycobiologically engineered Sindbis virus glycoprotein to target human DCs through the C-type lectin DC-SIGN (CD209) and also binds to the homologue murine receptor SIGNR1. Specificity of ID-VP02 for antigen-presenting cells in the mouse was confirmed through biodistribution studies showing that following subcutaneous administration, transgene expression was only detectable at the injection site and the draining lymph node. A single immunization with ID-VP02 induced a high level of antigen-specific, polyfunctional effector and memory CD8 T-cell responses that fully protected against vaccinia virus challenge. Upon homologous readministration, ID-VP02 induced a level of high-quality secondary effector and memory cells characterized by stable polyfunctionality and expression of IL-7Rα. Importantly, a single injection of ID-VP02 also induced robust cytotoxic responses against an endogenous rejection antigen of CT26 colon carcinoma cells and conferred both prophylactic and therapeutic antitumor efficacy. ID-VP02 is the first lentiviral vector which combines integration deficiency with DC targeting and is currently being investigated in a phase I trial in cancer patients. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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