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.

The development of efficient vaccines for the treatment of cancers in combination or not with other agents such as checkpoint inhibitors represents a major public health issue but remains a challenge. A dozen of vaccine drug products is expected to be marketed in the next few years. In this context, off-the-shelf and potent platforms are more attractive than individualized vaccines that are tailored to each patient in many aspects. We have recently developed a new cell-based vaccine approach named PDC*vac (formerly GeniusVac). This cell-based vaccine was developed thanks to the establishment, from leukemic PDC, of unique human PDC line (PDC*line). We have previously shown the potential of peptide-loaded PDC*line to induce strong and fully functional HLA-A*02:01-restricted anti-tumor immunity in vitro and in vivo (Aspord et al, 2010, 2012). PDC*mel (GenusVac-Mel4), our first product is currently developed for the treatment of melanoma patients (NCT01863108). The high efficiency of PDC*vac renders the strategy very attractive for further clinical developments in active immunotherapy field. Our aim is to optimize PDC*vac technology by passing use peptides and render the vaccine easier to manufacture. We engineered our PDC*line using retrovirus to force the endogenous expression of one or more tumor or viral antigenic peptides or whole tumor/viral proteins (gp100, tyrosinase, Melan-A, Mage-A3, CMVpp65, flu, EBV) that broaden the panel of antigens presented. Data obtaining with different polypeptide and protein gene coding constructions and the expansion of multi-specific antigen-specific T-cells at the same time will be presented. Moreover, we will present how we succeed to obtain 100% of efficacy in antigen presentation by the PDC*line engineered to express tumor proteins or polyepitopes. We have validated the use of retrovirus constructs to create a new generation of an “off-the-shelf” cancer vaccines highly potent to stimulate antitumor-specific T-cells. Citation Format: Joel Plumas, Kevin Lenogue, Alexandre Walencik, Jean-Paul Molens, Laurence Chaperot, Martin Pule. Generation of an off-the-shelf cell-based platform (PDC-vac) for active antitumor immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3686. doi:10.1158/1538-7445.AM2017-3686