Virological and Preclinical Characterization of a Dendritic Cell Targeting, Integration-deficient Lentiviral Vector for Cancer Immunotherapy
Open accessAbstract
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.
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Vaccinia virus, Zika virus, and human cytomegalovirus have been investigated in pre-clinical studies to test immune responses.
“Vaccinia virus [81], Zika virus [82], and human cytomegalovirus [83] have also been investigated in pre-clinical studies to test their immune responses.”
From Non-Integrating Lentiviral Vectors in Clinical Applications: A Glance Through (2022) · cites this paper as [81]
Citation [83] is attached to the human cytomegalovirus part of the sentence. The Results section, “Memory CD8 T Cells Induced by ID-VP02 Expand and Exhibit Antiviral Function” (page unavailable), describes preclinical immune-response testing with vaccinia virus, not human cytomegalovirus. Searches for human cytomegalovirus, HCMV, and CMV found no passage addressing that part of the claim. (LLM, conf=0.76)
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- Authors
- Odegard, J. M., Kelley-Clarke, B., Tareen, S. U., Campbell, D. J., Flynn, P. A., Nicolai, C. J., Slough, M. M., Vin, C. D., McGowan, P. J., Nelson, L. T., ter Meulen, J., Dubensky, T. W., & Robbins, S. H.
- Affiliations
- TRIA Bioscience (United States) (US)
- Juno Therapeutics (United States) (US)
- Aduro BioTech (United States) (US)
- Corresponding author
- Odegard, Jared M.
- Kelley-Clarke, Brenna
- Tareen, Semih U.
- Campbell, David J.
- Flynn, Patrick A.
- Nicolai, Christopher J.
- Slough, Megan M.
- Vin, Chintan D.
- McGowan, Patrick J.
- Dubensky, Thomas W.
- Robbins, Scott H.
- Venue
- Journal of Immunotherapy
- Published
- 2015-02
- Volume
- 38
- Issue
- 2
- Pages
- 41-53
- ISSN
- 1524-9557 (ISSN-L)
- PMC
- PMC4323576
- OpenAlex
- W2316952126
- Cited by
- 26
- References
- 37
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 1 · 2021: 1 · 2020: 6 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 7 · 2015: 4
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of Immunotherapy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r43ai087444-02)
- National Institute of Allergy and Infectious Diseases (1R43AI087444-01, R43 AI087444)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- dendritic cell targeting, cancer immunotherapy, DC-SIGN, antigen-presenting cells, CD8+ T cell responses, memory T cells, CD127, antitumor immunity, colon cancer, vaccinia virus challenge, tissue distribution, draining lymph nodes
- MeSH terms
- DC-Specific ICAM-3 Grabbing Nonintegrin, Animals, Carcinoma, Colonic Neoplasms, Cytotoxicity, Immunologic, Dendritic Cells, Genetic Engineering, Genetic Vectors, Glycoproteins, Humans, Immunologic Memory, Lymphocyte Activation, Mice, Inbred BALB C, Mice, Inbred C57BL, Protein Binding, Receptors, Cell Surface, Sindbis Virus, Vaccinia, Vaccinia virus, Viral Proteins, Cell Adhesion Molecules, Lentivirus, Immunotherapy, Adoptive, Virus Integration, Clinical Trials, Phase I as Topic, CD8-Positive T-Lymphocytes, Cancer Vaccines, Receptors, Interleukin-7, Lectins, C-Type, Cell Line, Tumor, Mice
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