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CD62L as target receptor for specific gene delivery into less differentiated human T lymphocytes
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  • Laura Kapitza,
  • Naphang Ho,
  • Thomas Kerzel,
  • Annika Frank M,
  • Frederic Thalheimer B,
  • Thomas Schaser,
  • Christian Buchholz,
  • Jessica Hartmann
Laura Kapitza
Paul-Ehrlich-Institut

Corresponding Author:laura@kreppendorf.de

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Naphang Ho
Paul-Ehrlich-Institut
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Thomas Kerzel
Paul-Ehrlich-Institut
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Annika Frank M
Paul-Ehrlich-Institut
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Frederic Thalheimer B
Paul-Ehrlich-Institut
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Thomas Schaser
Miltenyi Biotec BV & Co KG
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Christian Buchholz
Paul-Ehrlich-Institut
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Jessica Hartmann
Paul-Ehrlich-Institut
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Abstract

Chimeric antigen receptor (CAR) expressing T cells are a complex and heterogeneous gene therapy product with variable phenotype composition. A higher proportion of less differentiated CAR T cells is usually associated with improved antitumoral function and persistence. We describe here a novel receptor-targeted lentiviral vector (LV), named 62L-LV, that preferentially transduces less differentiated T cells marked by the L-selectin receptor CD62L, with transduction rates of up to 70% of CD4 + and 50% of CD8 + primary T cells. Remarkably, higher amounts of less differentiated T cells are transduced and preserved upon long-term cultivation using 62L-LV compared to VSV-LV. Interestingly, shed CD62L neither altered binding of 62L-LV particles to T cells nor impacted their transduction. Incubation of two days activated T lymphocytes with 62L-LV or VSV-LV for only 24 hours was sufficient to generate CAR T cells that controlled tumor growth in an NSG mouse model. The data prove that potent CAR T cells can be generated by short-term ex vivo exposure of primary cells to LVs. As a first vector type that preferentially transduces less differentiated T lymphocytes, 62L-LV has the potential to circumvent cumbersome selection of T cell subtypes and offers substantial shortening of the CAR T cell manufacturing process.
26 Sep 2022Submitted to Biotechnology and Bioengineering
27 Sep 2022Assigned to Editor
27 Sep 2022Submission Checks Completed
04 Oct 2022Reviewer(s) Assigned