ITOC 2026 | Dark antigen vaccines as a novel modality in cancer immunotherapy
Bernard Fox, PhD, Providence Cancer Institute, Portland, OR, comments the limitations of current vaccine strategies focused on neoantigens and the potential of targeting dark antigens, which are short-lived proteins that have a significant impact on gene regulation. A vaccine strategy concentrating on these dark antigens has been developed, which has shown promising results in clinical trials, especially in in patients with head and neck cancer. This interview took place at 12th Immunotherapy of Cancer (ITOC) Conference in Munich, Germany.
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Transcript
I talked about there was this big shift that is coming in our field. And I mentioned that we have a review coming out on this next week in JSTI. But the concept is that we’ve been looking at vaccines and we’ve been immunizing patients now for 60 years, and we’ve had evolution of different strategies, and our field has been focused on neoantigens for the last 10 to 15 years, and the clinical data has been disappointing in the advanced cancer setting...
I talked about there was this big shift that is coming in our field. And I mentioned that we have a review coming out on this next week in JSTI. But the concept is that we’ve been looking at vaccines and we’ve been immunizing patients now for 60 years, and we’ve had evolution of different strategies, and our field has been focused on neoantigens for the last 10 to 15 years, and the clinical data has been disappointing in the advanced cancer setting. And so we were looking at what else was there, and we had seen in preclinical data that there was something else that were good antigen targets. And it turned out that it appears that a big chunk of that were these dark antigens. So I talked a little bit about how that’s evolved, how we actually made a vaccine strategy that actually concentrated on short-lived proteins. And it turns out that many of these dark antigens, the reason they haven’t been found is because they get made, they have an impact on gene regulation, and then they get degraded. So their half-life is very short. And so they’re not around when a cancer cell dies and it releases its antigens. They’re not released, none of these antigens are picked up by the dendritic cells to stimulate immunity. So we talked about how we’ve been immunizing patients with these short-lived proteins. We now know that in our vaccine that has more than, has lots of antigens in it, has more than 400 dark antigens in it. And so we’ve been immunizing patients with that. It has appeared to be safe. And we’ve actually tripled response rates in patients with head and neck that have received combination immunotherapy with this. So we’ve tripled response rate, tripled complete response rate, tripled progression-free survival, and more than doubled overall survival in patients with head and neck. So we’re very excited about this. And we’ve been studying what the T cells are recognizing and that’s a big part of what my lab is focused on now.
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