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Virological and preclinical characterization of a dendritic cell targeting, integration-deficient lentiviral vector for cancer immunotherapy.


ABSTRACT: 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-7R?. 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.

SUBMITTER: Odegard JM 

PROVIDER: S-EPMC4323576 | biostudies-literature | 2015 Feb-Mar

REPOSITORIES: biostudies-literature

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Virological and preclinical characterization of a dendritic cell targeting, integration-deficient lentiviral vector for cancer immunotherapy.

Odegard Jared M JM   Kelley-Clarke Brenna B   Tareen Semih U SU   Campbell David J DJ   Flynn Patrick A PA   Nicolai Christopher J CJ   Slough Megan M MM   Vin Chintan D CD   McGowan Patrick J PJ   Nelson Lisa T LT   Ter Meulen Jan J   Dubensky Thomas W TW   Robbins Scott H SH  

Journal of immunotherapy (Hagerstown, Md. : 1997) 20150201 2


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  ...[more]

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