Tuesday, October 26
Times shown are in EST
Natural NeoAgs: Hiding in Plain Sight
09:30am - 12:00pm
There are a variety of different modalities used to identify the best neoantigen candidates as targets for anti-tumor treatments, as it is a critical step in determining the clinical success of these cancer immunotherapies. We have
developed a workflow that combines bioinformatic analysis with functional immunology to identify neoantigens through the T cell responses they induce, and find that nearly all cancer patients contain these in their peripheral repertoire.
This workshop will cover:
• Neoantigens can be functionally identified in nearly all cancer patients, regardless of TMB or histology
• Identified targets include shared driver mutations
La Jolla Institute for Immunology
Vaccination Against Shared Neoantigens Induced in Recurrent & Future Tumors
01:00pm - 03:30pm
To overcome the limitations of targeting random mutation-generated neoantigens, their inter- and intra-patient heterogeneity and paucity in most cancer patients, we are developing a novel vaccination concept whereby tumor cells are “marked” for vaccination by experimentally inducing (neo)antigens in the tumor cells in situ. The approach is to (a) “Decorate” tumor cells in situ with a common set of neoantigens (corresponding to the clinically relevant but elusive “clonal” mutationgenerated neoantigens) by downregulating the peptide transporter TAP via the systemic administration of a TAP siRNA that is targeted to the tumor cells by conjugation to a broad spectrum nucleolin binding aptamer, and (b) Vaccinate against the tumor-induced neoantigens by downregulating TAP in resident dendritic cells by systemic administration of a CpG oligonucleotide targeted TAP siRNA. Vaccination against TAP downregulation-induced antigens could represent a simple and common vaccination approach for most patients with cancer overcoming the main limitations of targeting mostly unique tumor-resident neoantigens
Professor of Immunology &
University of Miami
This workshop will explore:
• A common set of neoantigens that are induced in disseminated tumor lesions by tumor targeted siRNA mediated inhibition of the peptide transporter TAP.
• Vaccination against TAP downregulation induced neoantigens, by targeted inhibition of TAP in resident dendritic cells Inhibited tumor growth in transplantable and autochthonous murine tumor models that was superior to vaccination against mutation-derived neoantigens, and was devoid of measurable toxicity.
• Vaccination against induced antigens using one or two broadly applicable chemically synthesized oligonucleotides will also benefit the majority of patients that do not express or express too few mutation-derived neoantigens.