64P - Priming and expansion of neo-antigen specific-T cells thanks to an off-the-self cell-based drug product (64P)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Lymphomas
Cancer Aetiology, Epidemiology, Prevention
Haematologic Malignancies
Pathology/Molecular Biology
Presenter Joel Plumas
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors J. Plumas1, P. Alvez2, L. Chaperot3, D. Hannani1
  • 1R&d, PDC*Line Pharma, 38000 - Grenoble/FR
  • 2R&d, PDC*Line Pharma, 4000 - Liege/BE
  • 3Umr Uga-inserm-cnrs, EFS, 38701 - La Tronche/FR

Abstract

Background

PDC*vac is a patented technology relying on the use of PDC*line, a HLA-A*02:01+ plasmacytoïd Dendritic Cell (PDC) line, as a potent antigen presenting cell to strongly boost T cell responses both in vitro and in vivo. PDC*vac is composed of PDC*line pulsed with any desired HLA-A*02:01 restricted peptide, relevant for targeting a given cancer. Importantly, PDC*line can be also engineered with mRNA or viral vectors to endogenously express any desired antigens. PDC*vac superior potency and modularity represents a unique solution to overcome all the limitations of conventional therapeutic cancer vaccines. A strong body of preclinical data has demonstrated its unique ability to induce dramatic T cell expansions from naïve and memory CD8+ cells, against multiple antigens in the context of melanoma or lung cancer, both ex vivo from cord blood mononuclear cells, patients’ PBMC or Tumor Infiltrating lymphocytes (TILs), and in vivo in an innovative CD34+ humanized mouse model. Moreover, PDC*vac is being evaluated in a first-in-human phase I clinical trial in advanced melanoma.

Methods

Here, we aimed at exploiting PDC*vac properties for priming and expanding anti-neoantigen (neoAg) T cell responses from healthy donor naïve CD8+ T-cells.

Results

We demonstrated in this study that weekly stimulation by neoAg-pulsed PDC*line leads to sizeable expansion of antigen specific CD8+ T-cells from naïve precursors as soon as 14 days of co-culture, with a powerful expansion as day 21 (Fold increase: 50 to 150 compared to baseline). These results were obtained with cells purified form healthy donors’ mononuclear cells and 2 HLA-A*02:01 neoAg selected from the literature and identified in lung cancer or melanoma. This expansion is specific as no other antigen-specific T-cells were expanded. Moreover, these neoAg-specific T cells display functional activity as revealed by the expression of CD107 and IFNg secretion upon stimulation. Importantly, these cells are specific for the mutated form of the peptide and not the wild type form.

Conclusions

Altogether these data demonstrate that PDC*vac represents a powerful tool for assessing the immunogenicity of neo-epitopes in vitro as well as a powerful vaccine platform for personalized cancer immunotherapies.

Clinical trial identification

Legal entity responsible for the study

PDC*line Pharma

Funding

PDC*line Pharma

Disclosure

J. Plumas: Co-founder, CSO and employee of PDC*line Pharma. P. Alvez, D. Hannani: Employed by PDC*line Pharma. All other authors have declared no conflicts of interest.