Few days ago journal Science has published yet another study describing procedures how to identify tumor (melanoma)-specific immunogenic neo-antigens through exome-sequencing and combining peptide binding in silico and in vitro peptide recognition analysis.
There is no doubt that cancerous tissue can yield multiple neo-antigens derived from non-synonymous mutations. Hypothetically and practically (as this new study and others as well have shown), immune system can and is able to detect these minute differences in the mutated proteins. It appears that by combining current in silico algorithms such as NETMHC-3.4 with epitope presentation assays (in vitro assays) provide quite accurate list of potential immunogenic tumor peptides.
The authors in this new paper, for example, were able to identify and confirm in a complementary in vitro assays (T2 cell peptide binding assay and tandem minigene constructs expression assay in DM6 cell line) the presence of several neo-antigens in melanoma tissue derived from 3 patients.
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Re-injection of CD40L+TLR ligand matured, melanoma-peptide pulsed autologous dendritic cells back into patients yielded antigen-specific CD8 T cells expansion.
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This was a small Phase I clinical study to determine the safety of the DCs vaccine. Since science fundamentals are strong behind this trial (especially considering the authors focus on IL-12p70 producing DCs as a source of cellular vaccine), the results were expected. Of note, these 3 patients were treated with ipilimumab (humanized α-CTLA4 antibody) prior to the experiments described in this paper. It is not clear how this could have skewed the [positive] outcome of DC vaccine here. Anyway, successful tumor treatment would require simultaneous approach from several directions (DC vaccine, checkpoint inhibitors, small drug tyrosine inhibitors).
David Usharauli
David Usharauli
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