ObsERV identifies endogenous retroviruses lying dormant in our genomes
What is new?
We have discovered that endogenous retrovirus (ERVs) are a potential additional source of cancer antigens that can be used in personalized cancer immunotherapies to complement neoantigens. We have developed a bioinformatics platform that can a) identify ERVs based on sequencing data and b) design a personalized ERV antigen treatment. We have proof of concept that our method works in preclinical models.
For Evaxion, it enables us to facilitate and improve our personalized cancer immunotherapy pipeline. We believe that adding ERVs to PIONEER would potentially allow us to further improve the personalized cancer immunotherapies we design, targeting cancer indications that generally have fewer neoantigens. Evaxion has already started the discussion with the reg. authorities on how to include these targets in a personalized neoantigen treatment in future clinical trials.
What are ERVs?
Endogenous retroviruses (ERVs) are traces of ancient viruses embedded in our genome – viruses that infected our ancestors and incorporated themselves into our genome. This happened long ago (100K to millions of years). In normal cells, these traces of viruses do not do anything but lay dormant in the genome. Cancer cells, on the other hand, may express these old virus proteins, making them a perfect target for immunotherapy.
A vast potential/proof of concept
The discovery opens a new world of cancer indications that can be treated effectively with personalized neoantigen immunotherapy. For our current clinical programs, we hope to enhance PIONEER by adding ObsERV as an additional source of cancer antigens. This way, we can increase the overall quality of the (neo)antigens we find for each patient, thus increasing the efficacy of each personalized treatment.
Adding ObsERV to PIONEER means we can potentially treat patients with cancer types that could not be treated before, such as patients with a low tumor mutational burden (TMB), and thereby having few targetable neoantigens. Concretely, we show proof of concept in the preclinic that we can design ERV-based therapies that give durable tumor protection and mounts poly-functional T-cell responses (both CD8+ and CD4+). We further demonstrate that the number of expressed ERVs in a tumor is associated with response to immunotherapy in patients with low TMB. This supports that ERVs constitute an additional antigen source for cancer immunotherapy and that our preclinical findings may translate to the clinic. A large-scale analysis of several cancer types demonstrates that cancers with low TMB may still express a large number of ERVs. In short, this means that immunotherapy can be effective in a much larger population.
Endogenous viral elements could be a key component to overcome a fundamental limitation of immunotherapy, namely, identifying good neoantigens in patients afflicted by cancers with few mutations. Our findings spark hope for bringing tailored therapies to a lot more cancer patients than previously anticipated.
Professor Anthony W. Purcell
Evaxion’s unique approach
Endogenous retroviruses (ERVs) have been described in the literature as potential antigens in the past, and other companies are developing cancer vaccines based on ERVs. However, those approaches rely on finding ERV antigens that are shared amongst many patients, which heavily limits the number of patients that can be treated. Our approach is new because we determine which ERVs are relevant for each patient in a personalized manner. We can identify protective antigens by ObsERV and incorporate them into a personalized vaccine. To our knowledge, we are also the first to discover that the presence of ERVs in cancers can be used to predict a patient’s response to immunotherapy.
Endogenous viral elements may enable the development of potent personalized therapies for patients afflicted by cancers with few targetable mutations. These new cancer targets could unlock a wealth of treatment possibilities.
Dr. Pouya Faridi
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