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Cited by 62Virus-based gene therapy researchImmunotherapy and Immune ResponsesCAR-T cell therapy research

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Reprogramming T Lymphocytes for Melanoma Adoptive Immunotherapy by T-Cell Receptor Gene Transfer with Lentiviral Vectors

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Bobisse, Sara, Rondina, Maria, Merlo, Anna, Tisato, Veronica, Mandruzzato, Susanna, Amendola, Mario, Naldini, Luigi, Willemsen, Ralph A., Debets, Reno, Zanovello, Paola, Rosato, Antonio·2009·Cancer Research
DOI 10.1158/0008-5472.can-09-0494

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Abstract

T-cell receptor (TCR) gene transfer for cancer immunotherapy is limited by the availability of large numbers of tumor-specific T cells. TCR α and β chains were isolated from a highly lytic HLA-A2–restricted cytotoxic T lymphocyte (CTL) clone recognizing the melanoma-associated Melan-A/MART-1 antigen and inserted into a lentiviral vector carrying a bidirectional promoter capable of robust and coordinated expression of the two transgenes. Lentiviral vector–based gene delivery systems have shown increased transfer efficiency and transgene expression compared with the widely used γ-retroviral vectors. This vector performed more efficiently than a γ-retrovirus–based vector containing the same expression cassette, resulting in a T-cell population with 60% to 80% of transgenic TCR expression with mainly CD8+ intermediate effector phenotype. Transgenic T cells specifically produced cytokine in response to and killed antigen-expressing melanoma cells, retained an overlapping functional avidity in comparison with the TCR donor CTL clone, and exerted significant therapeutic effects in vivo upon adoptive transfer in melanoma-bearing severe combined immunodeficient mice. Optical imaging showed their accumulation in the tumor site. Overall, our results indicate that lentiviral vectors represent a valid tool for stable and high-intensity expression of transgenic TCR and support clinical exploitation of this approach for therapeutic application. [Cancer Res 2009;69(24):9385–94]

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  • A lentiviral vector exhibited better transduction efficiency than a gammaretroviral vector in transducing T cells with a TCR targeting the Melan-A/MART-1 antigen.

    “In addition, a lentiviral vector exhibited better transduction efficiency than a gammaretroviral vector in transducing T cells with a TCR targeting the Melan-A/MART-1 antigen [73]”

    From Clinical use of lentiviral vectors (2018) · cites this paper as [73]

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Metadata

Authors
Bobisse, S., Rondina, M., Merlo, A., Tisato, V., Mandruzzato, S., Amendola, M., Naldini, L., Willemsen, R. A., Debets, R., Zanovello, P., & Rosato, A.
Affiliations
University of Padua (IT)
Corresponding author
Rosato, Antonio
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2009-12-14
Volume
69
Issue
24
Pages
9385-9394
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-09-0494
OpenAlex
W1990035544
Cited by
62
References
1
Citations by year
2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 8 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 5 · 2013: 5 · 2012: 4
FWCI
4.26
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Cancer Research (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
Funders
Ministero della Salute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
Keywords
T cell receptor gene transfer, lentiviral vectors, melanoma, adoptive immunotherapy, bidirectional promoter, gammaretroviral vectors, transgenic T cells, tumor-specific T cells, SCID mice
MeSH terms
Animals, Epitopes, Antigens, Neoplasm, Female, Genetic Vectors, Humans, Immunologic Memory, Leukocytes, Mononuclear, Melanoma, Neoplasm Proteins, T-Lymphocytes, Transduction, Genetic, HLA-A2 Antigen, Lentivirus, Immunotherapy, Adoptive, Mice, SCID, Receptors, Antigen, T-Cell, alpha-beta, Jurkat Cells, Genes, T-Cell Receptor alpha, Genes, T-Cell Receptor beta, Mice, MART-1 Antigen

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