425. Lentiviral Vector Platforrm To Develop Anti-Cancer Immunotherapies
Authors: Deborah Revaud, Sophie Agaugue, Emeline Sarry, Ana Bejanariu, Cecile Bauche
Journal: Molecular Therapy (2015)

In immunotherapy of cancer, different vaccination strategies have been developed and evaluated in clinical trials, e.g. monoclonal antibodies, injection of DNA, peptides, proteins, autologous cells (tumoral cells, dendritic cells (DC) or T cells) processed in vitro or even direct injection of modified viral vectors. THERAVECTYS is a Paris-based, privately-owned, fully integrated discovery & clinical development biotech company, developping lentiviral vectors for human vaccination and immunotherapy applications. THERAVECTYS' vaccine candidates based on a proprietary lentiviral vector technology enable a direct vaccination mechanism in patients by inducing a broad, intense and long-lasting T cell mediated response. Theravectys' technology presents several advantages compared to these various vaccination approaches: -Our lentivectors encompasse up to 15kb DNA, the resulting polypeptide hence targeting a combination of different antigens which mobilizes different actors of the anti-tumor immune system-No selection of patients is needed according to HLA haplotype since epitopes are physiologically processed in vivo.-Unlike all other vaccination approaches, this technology allows the transduction of non-dividing cells such as DC, the most potent antigen-presenting cells (APC) of the immune system.-Break of immunotolerance: lentivectors not only provide sufficient amounts of antigens to DCs but also ensure an efficient processing and prolonged presentation of the antigens, an efficient maturation of DCs that possess all the stimulating abilities to induce an efficient activation of T cells-Non replicative and non persistent lentivectors-antigen expressing cells and transduced cells are eliminated by the immune response elicited after injection.-Direct injections in patients, without ex vivo process of autologous cells.-Different pseudotypes of lentivectors are developed to avoid specific immune reaction against the vector during boost injection(s).-Vaccination with lentiviral vectors are more potent and efficient than DNA or peptide or protein vaccination. The phase I/II clinical trial with our first vaccine candidate has been completed in HIV-infected patients. The vaccine is safe, as demonstrated by the clinical trial ongoing in 38 patients (no Serious Adverse Events have been reported during the trial). The interim analysis of the immunological data from the first two cohorts of patients performed by THERAVECTYS demonstrates the ability of the vaccine candidate to elicit multi-specific and poly-functional CD4+ and CD8+ cellular immune responses in vaccinated patients, even at the lowest dose. The interim analysis of this trial supports the potential of the lentiviral vector platform developed by THERAVECTYS for the future development of therapeutic vaccines and immunotherapies in oncology and infectious diseases. As a second indication, THERAVECTYS is developing an anti-HTLV-1 vaccine candidate to treat patients who have developed a virally-induced adult T cell leukemia. This vaccine candidate should enter into the clinics in mid-2015. Other indications in the pipeline are urogenital cancers, triple-negative breast cancer, EBV-induced nasopharyngeal cancers, HPV-induced cancers (cervix, oropharyngeal and anal cancers) and multiple myeloma.