HERVolution Publishes Translational Tumor Data Supporting HERV-K as an "Off-the-Shelf" Cancer Vaccine Target

Peer-reviewed study finds HERV-K antigen-coding sequences expressed in all 207 advanced non-small cell lung cancer tumors analyzed, and reports that lung cancer cell lines depend on HERV-K for growth and survival

COPENHAGEN, Denmark and NEW YORK, Nov. 5, 2026 /PRNewswire/ -- HERVolution Therapeutics ApS, a biotechnology company pioneering human endogenous retrovirus (HERV)-targeting immunotherapies for oncology, metabolic diseases, cellular senescence and longevity, today announced the publication of peer-reviewed data supporting human endogenous retrovirus K (HERV-K) as a tumor antigen in non-small cell lung cancer (NSCLC) — the indication selected for the Company's planned first-in-human study of HTX-IPT001.

The study, titled "Endogenous Retrovirus-Targeted Immunotherapy for Non-Small Cell Lung Cancer Supported by Cellular HERV-K Expression, Dependency and Efficacy of ERV Therapy in a Murine Model," appears open access in the International Journal of Molecular Sciences and is available at https://doi.org/10.3390/ijms27219717.

Where the Company's recent platform publication described how the HERV-K envelope can be engineered to break immune tolerance, this study addresses the indication question: whether HERV-K is present, targetable and difficult for tumors to discard in advanced NSCLC specifically.

HERV-K antigen sequences are expressed across advanced NSCLC

Using total RNA sequencing of 207 biopsies from patients with advanced, predominantly pretreated NSCLC, the authors detected expression of HERV-K Gag and envelope (Env) antigen-coding sequences across the cohort. Every tumor analyzed expressed at least one such sequence, and expression was typically distributed across multiple loci rather than confined to a single one. This redundancy is relevant to a vaccine strategy, because it reduces the likelihood that a tumor can escape a HERV-K-directed immune response by silencing any one sequence.

Genetic redundancy of dark genome loci enables an off-the-shelf cancer vaccine

This redundancy also sets HERV-K apart from the personalized approaches that dominate current cancer vaccine development. Personalized mRNA vaccines must be custom-designed around each patient's private tumor mutations — a set of targets unique to that patient, and one a tumor can edit away under immune pressure. HERV-K, by contrast, is encoded in the human genome itself, with more than 90 full-length loci shared by every patient. A single off-the-shelf product can therefore address the antigen in any HERV-K-expressing tumor, and because expression is spread across many loci, there is no single sequence whose loss would allow the tumor to escape.

NSCLC cell lines show dependency on HERV-K

Knockdown of HERV-K in five NSCLC cell lines impaired proliferation and survival in each line tested. The authors present these as initial dependency experiments, each conducted as a single independent experiment, and further work will be required to establish the mechanism and generality of the effect. If confirmed, the observation would indicate that HERV-K expression is not an incidental feature of these tumors but one the cells retain under selective pressure.

Antigen expression is retained under cytokine and chemotherapy pressure

HERV-K protein was detected in all five cell lines. Exposure to inflammatory cytokines and to cisplatin altered HERV-K protein levels, but antigen expression was retained and in some conditions increased. The same exposures consistently raised PD-L1 expression. Separately, a single envelope locus, HERV-K102, was associated with interferon signaling and antigen-presentation programs, suggesting it may mark an interferon-active tumor state. These are observational associations in tumor transcriptomes and in vitro systems, and have not been tested prospectively.

Preclinical proof-of-concept for ERV-targeted immunotherapy

In a murine tumor model, immunization against an endogenous retrovirus antigen conferred significant protection against tumor challenge. Late therapeutic immunization combined with anti-PD-L1 treatment produced complete tumor regression in a subset of animals. Importantly, these experiments used a murine endogenous retrovirus surrogate antigen rather than HERV-K itself, because HERV-K is not present in the mouse genome. The authors therefore describe the result as proof-of-concept for ERV-targeted immunotherapy in a murine surrogate system, not as direct evidence of HERV-K-targeted efficacy. The study was not powered a priori, and these findings are preclinical.

 "Our platform publication established that HERV-K can be rationally engineered to break tolerance. This study answers the question that follows from it — why lung cancer, and why now. It also underlines a structural advantage of the target: because HERV-K is written into every human genome at more than 90 loci, it is an off-the-shelf antigen — one product for every patient, rather than a vaccine redesigned around each patient's tumor, and one a tumor cannot discard by silencing a single sequence. It places the target rationale for our planned first-in-human study in the open literature, where investigators, partners and the wider field can assess it on its merits."
— J. Robert Coleman, PhD, MBA, Chief Executive Officer, HERVolution Therapeutics

The study was conducted by HERVolution Therapeutics in collaboration with the University of Copenhagen and Copenhagen University Hospital – Rigshospitalet. It was supported by the European Innovation Council Accelerator (grant 190120397) and the EUREKA Eurostars Programme (grant 3150-00110B). Human samples were collected under ethics approval H-16046103 with written informed consent from all patients; animal work was approved by the Danish Animal Experimentation Inspectorate (2024-15-0201-01692).

About HTX-IPT001 and the planned first-in-human study

HTX-IPT001 is an adenovirus-based advanced therapy medicinal product (ATMP) encoding an engineered HERV-K antigen. HERVolution is preparing a first-in-human study of HTX-IPT001 in patients with NSCLC as well as in metabolic disease, with both planned to begin in 2027. The studies has not yet begun and remains subject to regulatory and ethics approval. HTX-IPT001 is an investigational candidate and is not approved for use in any indication.

About HERVolution Therapeutics

HERVolution Therapeutics is a biotechnology company pioneering human endogenous retrovirus (HERV)-targeting immunotherapies for oncology, metabolic diseases, and longevity. HERVs are ancient viral sequences embedded in the human genome that become reactivated in cancer and other diseases of aging. By directing the immune system against HERV-derived antigens, HERVolution aims to deliver a new class of senolytic therapies across multiple indications where HERV reactivation and cellular senescence contribute to disease biology. The Company's lead program, HTX-IPT001, is advancing toward first-in-human studies in oncology and metabolic disease. For more information, please visit hervolutiontx.com. Follow us on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements, including statements regarding the planned initiation, design, timing and conduct of HERVolution's first-in-human study of HTX-IPT001 and the potential of HERV-targeted immunotherapy. Such statements are based on current expectations and are subject to risks and uncertainties, including the outcome of regulatory and ethics review, manufacturing and supply, clinical trial enrollment, and the risk that preclinical findings do not translate to humans. Preclinical results are not predictive of results in clinical studies. HERVolution undertakes no obligation to update these statements except as required by law.

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