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Engineering a Human Plasmacytoid Dendritic Cell-Based Vaccine to Prime and Expand Multispecific Viral and Tumor Antigen-Specific T-Cells

Abstract : Because dendritic cells are crucial to prime and expand antigen-specific CD8+ T-cells, several strategies are designed to use them in therapeutic vaccines against infectious diseases or cancer. In this context, off-the-shelf allogeneic dendritic cell-based platforms are more attractive than individualized autologous vaccines tailored to each patient. In the present study, a unique dendritic cell line (PDC*line) platform of plasmacytoid origin, already used to prime and expand antitumor immunity in melanoma patients, was improved thanks to retroviral engineering. We demonstrated that the clinical-grade PDC*line, transduced with genes encoding viral or tumoral whole proteins, efficiently processed and stably presented the transduced antigens in different human leukocyte antigen (HLA) class I contexts. Moreover, the use of polyepitope constructs allowed the presentation of immunogenic peptides and the expansion of specific cytotoxic effectors. We also demonstrated that the addition of the Lysosome-associated membrane protein-1 (LAMP-1) sequence greatly improved the presentation of some peptides. Lastly, thanks to transduction of new HLA molecules, the PDC platform can benefit many patients through the easy addition of matched HLA-I molecules. The demonstration of the effective retroviral transduction of PDC*line cells strengthens and broadens the scope of the PDC*line platform, which can be used in adoptive or active immunotherapy for the treatment of infectious diseases or cancer.
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https://www.hal.inserm.fr/inserm-03335650
Contributor : Elizabeth Bernardo <>
Submitted on : Monday, September 6, 2021 - 1:49:38 PM
Last modification on : Thursday, September 9, 2021 - 3:22:05 AM

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Kevin Lenogue, Alexandre Walencik, Karine Laulagnier, Jean-Paul Molens, Houssem Benlalam, et al.. Engineering a Human Plasmacytoid Dendritic Cell-Based Vaccine to Prime and Expand Multispecific Viral and Tumor Antigen-Specific T-Cells. Vaccines, MDPI, 2021, 9 (2), pp.141. ⟨10.3390/vaccines9020141⟩. ⟨inserm-03335650⟩

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