ITOC 2026 | Evaluating the benefits dark genome vaccines in trials for solid tumors
Bernard Fox, PhD, Providence Cancer Institute, Portland, OR, describes the advantages of dark genome vaccines, highlighting their potential to be shared across patients and their role in driving the cancer malignant phenotype, with some dark antigens having tumor-promoting activity. Preliminary research has identified a limited number of these shared dark antigens, and that clinical trials, such one assessing DPV-001, have shown promising results. This interview took place at 12th Immunotherapy of Cancer (ITOC) Conference in Munich, Germany.
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Transcript
That’s a great question, and I think there are a number of advantages. So first, the personalized cancer vaccines that we’ve been seeing for the last decade, where people have had to have their tumor biopsies taken, they have to be sequenced, you have to identify all the potential neoantigens, then you have to make the vaccine. None of that is going to happen, I think, with the dark genome vaccines, because it appears that there’s a limited number of these, and they appear to be shared...
That’s a great question, and I think there are a number of advantages. So first, the personalized cancer vaccines that we’ve been seeing for the last decade, where people have had to have their tumor biopsies taken, they have to be sequenced, you have to identify all the potential neoantigens, then you have to make the vaccine. None of that is going to happen, I think, with the dark genome vaccines, because it appears that there’s a limited number of these, and they appear to be shared. In a report that we had at CTSI in November of 2025, we looked at two patients with head and neck cancer, and for the HLA-B44 haplotype, there were 70 dark antigens that were shared between these two different patients. And as we went to other HLA’s, there were other numbers that weren’t quite as high as the HLA-B44. But it gives me great confidence that these dark antigens are going to be shared because it appears that these dark antigens, in addition to being things that are not normally expressed in normal tissue, they’re things that appear to have biological function that are driving the cancer malignant phenotype. And some really nice work from Prendergast, who I have at University of Michigan, identifying in a recent paper 57 of these dark proteins, microproteins, that actually have tumor-promoting activity. So I think it’s a really exciting time. The second part of your question is going to be, you know, I think translating this to the clinic, right? How are we going to do this? We’ve already been doing this with a biotech that we spun out, UBI-VAC, or possibly UVAC they have a clinical trial with DPV001, and working with Insight they’ve, as I mentioned I think a second ago, they’ve tripled response rates. So I think this is possible, and I think it’s possible to have things that are going to be off the shelf, and I think it’s going to accelerate the clinical applicability and reduce costs, do a lot of other things that are going to be beneficial for the system.
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