Copenhagen, Denmark, and New York, United States, October 28, 2026
HERVolution Therapeutics, a biotechnology company developing human endogenous retrovirus (HERV)-targeting immunotherapies, has published new foundational research demonstrating how rationally engineered HERV-K antigens can overcome immune tolerance and stimulate immune cells to recognise cancer cells. The findings, published in the peer-reviewed Journal of Translational Medicine, provide scientific support for the company’s approach to developing next-generation cancer immunotherapies. The research also identified HERV-K expression across a broad range of cancer types, strengthening its potential as a therapeutic target. The study analysed tumour data from 1,353 patients across 43 cancer types, demonstrating widespread expression of human endogenous retrovirus-K (HERV-K). The publication further describes the protein-engineering strategy behind HERVolution’s lead investigational programme, IPT-001, which is being developed to stimulate immune responses against cancer-associated HERV-K antigens. The findings represent an important research milestone in exploring previously underutilised biological targets for cancer treatment.
HERV-K Expression Identified Across 43 Cancer Types
The study investigated the potential of HERV-K (HML-2) as a broadly relevant tumour-associated antigen. Human endogenous retroviruses are ancient viral sequences incorporated into the human genome during evolution. Although most remain inactive, certain HERV sequences can become reactivated in cancer cells and other disease conditions. Researchers analysed RNA sequencing data from 1,353 patients enrolled in the Copenhagen Prospective Personalized Oncology (CoPPO) study, including individuals with advanced and predominantly previously treated cancers. The analysis identified HERV-K expression across nearly all cancer types examined, covering 43 cancer types, cancers of unknown primary and unclassified tumours. A majority of patients demonstrated more than 100 HML-2 reads per million total reads. These observations suggest that HERV-K could provide a potential target for immunotherapy development across multiple cancer indications rather than being restricted to a single tumour type. The findings are particularly relevant because identifying tumour-associated antigens that are consistently expressed across different cancers remains an important objective in oncology research. The broad expression profile of HERV-K supports further investigation into its potential as a shared cancer immunotherapy target.
Engineered HERV-K Antigens Stimulate Immune Responses
A major scientific finding involved the modification of the HERV-K envelope protein to improve its ability to activate the immune system. Researchers identified a specific amino acid substitution, Q525A, designated ISDmut, within the protein’s putative immunosuppressive domain. The modification enhanced NF-κB signalling and increased antigen expression and presentation in human monocyte-derived dendritic cells. These specialised immune cells play an important role in identifying foreign or abnormal cellular material and activating T-cell responses. In laboratory experiments, dendritic cells carrying the engineered HERV-K antigen stimulated the expansion of both CD4-positive helper T cells and CD8-positive cytotoxic T cells from healthy human donors. In an HLA-matched experimental setting, the expanded CD8-positive T cells recognised HERV-K-expressing non-small cell lung cancer cells. This provides evidence that human immune cells can be trained to recognise cancer cells carrying the targeted antigen. The researchers also evaluated the engineered antigen using adenoviral and messenger RNA lipid nanoparticle delivery systems. These approaches generated immune responses in mice, HERV-K transgenic animals and non-human primates. The results demonstrate the potential of protein engineering to overcome immune tolerance and improve recognition of cancer-associated antigens.
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IPT-001 Programme Advances HERVolution’s Oncology Strategy
The published findings provide the scientific foundation for IPT-001, HERVolution Therapeutics’ lead investigational cancer immunotherapy programme. The company’s approach is designed to make HERV-derived antigens more visible to the immune system by modifying their immunosuppressive characteristics. The research also evaluated antitumour activity in a mouse model of metastatic renal carcinoma expressing HERV-K. Animals receiving prime-boost immunisation with the engineered antigen demonstrated significantly improved clearance of lung metastases and better overall survival compared with control animals. The study also reported additional benefits when the experimental immunisation was combined with anti-PD-1 treatment. These findings provide an important rationale for investigating potential combinations with existing immunotherapy approaches. HERVolution’s research was conducted in collaboration with the University of Copenhagen, Copenhagen University Hospital–Rigshospitalet, Herlev Hospital, IPB University and Revvity Gene Delivery. The company is advancing IPT-001 towards first-in-human clinical studies in oncology, with non-small cell lung cancer among its areas of interest. Importantly, the reported findings are preclinical and laboratory-based; IPT-001 has not yet established clinical safety or efficacy in human patients. Further research and clinical trials will be necessary to determine whether engineered HERV-K antigens can translate into effective cancer treatments. The publication nevertheless represents a significant scientific step towards developing new immunotherapy strategies targeting previously overlooked elements of the human genome.
Source: HERVolution Therapeutics press release
