PMID- 33578850 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210316 IS - 2076-393X (Print) IS - 2076-393X (Electronic) IS - 2076-393X (Linking) VI - 9 IP - 2 DP - 2021 Feb 10 TI - Engineering a Human Plasmacytoid Dendritic Cell-Based Vaccine to Prime and Expand Multispecific Viral and Tumor Antigen-Specific T-Cells. LID - 10.3390/vaccines9020141 [doi] LID - 141 AB - 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. FAU - Lenogue, Kevin AU - Lenogue K AD - Immunobiology and Immunotherapy of Chronic Diseases, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Universite Grenoble Alpes, 38700 La Tronche, France. AD - PDC*line Pharma, 38701 Grenoble, France. AD - Research and Development laboratory, Etablissement Francais du Sang Auvergne-Rhone-Alpes, 38701 Grenoble, France. FAU - Walencik, Alexandre AU - Walencik A AD - Immunobiology and Immunotherapy of Chronic Diseases, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Universite Grenoble Alpes, 38700 La Tronche, France. AD - HLA Laboratory, Etablissement Francais du Sang Centre-Pays de la Loire, 44011 Nantes, France. FAU - Laulagnier, Karine AU - Laulagnier K AD - PDC*line Pharma, 38701 Grenoble, France. FAU - Molens, Jean-Paul AU - Molens JP AD - Immunobiology and Immunotherapy of Chronic Diseases, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Universite Grenoble Alpes, 38700 La Tronche, France. AD - Research and Development laboratory, Etablissement Francais du Sang Auvergne-Rhone-Alpes, 38701 Grenoble, France. FAU - Benlalam, Houssem AU - Benlalam H AD - CRCINA, INSERM, Universite d'Angers, Universite de Nantes, 44011 Nantes, France. FAU - Dreno, Brigitte AU - Dreno B AD - Onco-Dermatology Department, CHU Nantes, CIC 1413, CRCINA, Universite de Nantes, 44093 Nantes, France. FAU - Coulie, Pierre AU - Coulie P AD - De Duve Institute, Universite Catholique de Louvain, B-1200 Brussels, Belgium. FAU - Pule, Martin AU - Pule M AD - Cancer Institute, University College London, London WC1E 6BT, UK. FAU - Chaperot, Laurence AU - Chaperot L AUID- ORCID: 0000-0002-1479-9410 AD - Immunobiology and Immunotherapy of Chronic Diseases, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Universite Grenoble Alpes, 38700 La Tronche, France. AD - Research and Development laboratory, Etablissement Francais du Sang Auvergne-Rhone-Alpes, 38701 Grenoble, France. FAU - Plumas, Joel AU - Plumas J AUID- ORCID: 0000-0002-5005-4301 AD - Immunobiology and Immunotherapy of Chronic Diseases, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Universite Grenoble Alpes, 38700 La Tronche, France. AD - PDC*line Pharma, 38701 Grenoble, France. AD - Research and Development laboratory, Etablissement Francais du Sang Auvergne-Rhone-Alpes, 38701 Grenoble, France. AD - Cancer Institute, University College London, London WC1E 6BT, UK. LA - eng GR - FP7-PEOPLE-2009-IEF Proposal n degrees 251033 - Acronym: PDC Therapy/FP7 People: Marie-Curie Actions/ PT - Journal Article DEP - 20210210 PL - Switzerland TA - Vaccines (Basel) JT - Vaccines JID - 101629355 PMC - PMC7916617 OTO - NOTNLM OT - cancer diseases OT - immunotherapy OT - infectious diseases OT - plasmacytoid dendritic cells OT - vaccination COIS- Joel Plumas has been the Chief Scientific Officer of PDC*line Pharma since 2014. Pierre Coulie is a member of the Scientific Advisory Board of PDC*line Pharma. EDAT- 2021/02/14 06:00 MHDA- 2021/02/14 06:01 PMCR- 2021/02/10 CRDT- 2021/02/13 01:01 PHST- 2021/01/07 00:00 [received] PHST- 2021/02/03 00:00 [revised] PHST- 2021/02/08 00:00 [accepted] PHST- 2021/02/13 01:01 [entrez] PHST- 2021/02/14 06:00 [pubmed] PHST- 2021/02/14 06:01 [medline] PHST- 2021/02/10 00:00 [pmc-release] AID - vaccines9020141 [pii] AID - vaccines-09-00141 [pii] AID - 10.3390/vaccines9020141 [doi] PST - epublish SO - Vaccines (Basel). 2021 Feb 10;9(2):141. doi: 10.3390/vaccines9020141.