At the virtual TIDES: Oligonucleotide and Peptide Therapeutics conference in September 2020, Dr. Daniel deOliveira from Genocea Biosciences explained how his company moved towards differentiated immunotherapies through precision antigen selection with their personalized immune response profiling platform ATLAS, which stands for AnTigen Lead Acquisition System.
This is an extract taken from the ebook 'Personalized Peptide Vaccines & Therapies'. Read the full article here.
The personalized immune response profiling platform
This platform mainly comprises two programs: GEN-009, a neoantigen vaccine for which a Phase 1/2a clinical trial is ongoing; and GEN-011, a neoantigen-specific cell therapy using T cells derived from peripheral blood. There is also in the Genocea Biosciences discovery pipeline the GEN-010 platform, which is a follow-on neoantigen cancer vaccine, still in Pre-IND phase; and, shared antigen cancer vaccines and vaccines for cancers of viral origin (e.g., Epstein-Barr virus).
The focus of the ATLAS profiling platform is neoantigen selection, that is the identification of mutations that allow the cancer cells to propagate and invade tissues in a thoroughly biological sense. ATLAS empirically selects the relevant neoantigens of tumour-specific T cell responses in patient and tumour-relevant conditions. Tumour biopsies together with saliva samples from patient donors are sent for Next-Generation Sequencing (NGS) analysis.
From that inquiry, plasmids are then selected for every candidate neoantigen and are inserted in a e-coli vector. At the same time, from a blood sample of the patient, a selection of dendritic cells is made, together with CD4+ and CD8+ T-cells.
Selecting the dendritic cells
Afterwards, the dendritic cells sampled are treated with the neoantigen bacterial vectors, and the ones with positive immune responses to the patient CD8+ T-cells are then selected for autologous treatment. From this personalized experimental analysis, two read-outs can be made: (1) is it a true antigen or not; and, (2) is it stimulatory or inhibitory?
As such, personalized tumour mutations presented to dendritic cells are digested and offered through MHC bound peptides that are recognized by T cells. If, from this presentation, an anti-tumour CD8+ T-cell reaction based on a normalized cytokine concentration (IFN-gamma) response is made, then a new stimulatory neoantigen has been positively selected. If, on the other hand, a negative normalized cytokine concentration (IFN-gamma) response is obtained in CD4+ T-cells, then an inhibitory antigen (Inhibigens’) is confidently obtained.
What this means is that this specific inhibigen is removed from the patient vaccine neoantigen pool, because it inhibits the immune response against the cancer.
This is an extract taken from the ebook 'Personalized Peptide Vaccines & Therapies'.