New UK startup pursues off-the-shelf CAR-T, cancer vaccines through 'dark antigens'
Scientists unfurling the human genome at the turn of the century came across many surprises but perhaps nothing as shocking as the percentage of the genome that didn’t appear to code for anything. Around 2% wrote proteins and the rest appeared to be “junk,” “dark,” or, as the New York Times then put it, “the apparent product of a typing pool of drunken baboons. ”
Armed with the supposition baboons hadn’t created human DNA, many scientists have the spent the prevailing two decades figuring out what the so-called junk DNA is for or how it got there. One startup out of the UK is now bypassing part of that question and attempting to leverage segments of “dark” DNA for cancer vaccines and immunotherapies.
Ervaxx launched out of London with $17.5 million in seed and Series A funding on the promise that some non-coding DNA in fact codes proteins in cancer cells and that those proteins could be targets for cancer vaccines and off-the-shelf CAR–T. The funding is from SV Health Investors and an undisclosed global pharmaceutical company. They’ve dubbed the tech “Dark Antigens” — after the dark genome and a play on cosmological dark matter, the vast amount of matter in the universe we’re pretty sure is there but remains invisible and largely inscrutable.
“What we found is a set of sequences in the genome that are selectively transcribed and translated in cancer and not in normal cells,” CEO Kevin Pojasek told Endpoints News. “I think it’s scientifically fascinating that we’re sitting here in 2019 and finding new proteins in cancer cells and from a therapeutic perspective, it could make great antigens or neo-antigens for cell therapy.”
Ervaxx’s platform emerged out of a relatively well-understood part of the dark genome, endogenous retroviruses (ERV). Over millennia or eons of infecting humans and our mammalian ancestors, these ancient viruses incorporated themselves into our DNA and left a footprint that accounts for about 8% of human genetic code. Ervaxx’s pitch is that the rapid damage cancer causes to tumor DNA can lead proteins in these normally dead regions to be coded.
It’s not clear what – if anything – these proteins do, but Pojasek said they can function as an antigen target for tumor cells. He said their research showed that they are already detectable to naive tumor cells, in theory allowing Ervaxx to use a vaccine or a CAR-T process to then amp-up the immune response.
Because the same antigens appear to be present in different people, they might allow for an off-the-shelf CAR-T approach, although Ervaxx is also pursuing a vaccine and classic CAR-T strategy. Its lead program is a vaccine for melanoma, with other therapies in the works for non-small cell lung cancer, ovarian cancer and breast cancer, among others. They hope to ward off resistance to any potential therapy by triggering an immune response against multiple dark antigens.