HERVolution Publishes Foundational Data Demonstrating Rationally Engineered HERV-K Antigens Can Break Immune Tolerance and Train Immune Cells to Target Cancer Cells

Peer-reviewed study describes the rationally engineered envelope modification underpinning HERVolution's lead program, IPT-001, and detects HERV-K expression across the majority of 43 cancer types in 1,353 patients

COPENHAGEN, Denmark and NEW YORK, Oct. 28, 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 foundational data on its HERV-K platform in the peer-reviewed Journal of Translational Medicine. The article, titled "Engineering human endogenous retrovirus-K for improving immunogenicity and broad cancer targeting," is available online at https://doi.org/10.1186/s12967-026-09012-1.

The publication is a comprehensive data set detailing the science behind HERVolution's technology. Using patient tumor data, the manuscript first defines the rationale for selecting HERV-K (HML-2) as a broad tumor antigen. It then describes the rational protein engineering that breaks human immune tolerance and renders HERV-K visible to the immune system, and finally reports immunogenicity and anti-tumor activity across human cells, mice, transgenic mice, and non-human primates.

HERV-K expression is broad across human cancers

Analysing RNA sequencing data from 1,353 patients with advanced, predominantly pre-treated cancer enrolled in the Copenhagen Prospective Personalized Oncology study (CoPPO, NCT02290522), the authors detected HERV-K expression in nearly all cancer types examined, with the majority of patients showing more than 100 HML-2 reads per million total reads across 43 cancer types, cancers of unknown primary, and unclassified tumors. The finding extends earlier, indication-specific reports and supports the breadth of the opportunity for a HERV-K-directed therapy.

A single engineered substitution converts a tolerated self-antigen into an immunogen

Through a systematic mutational screen of the putative immunosuppressive domain (ISD) of the HERV-K envelope protein, the team identified the Q525A substitution — termed ISDmut — as the most potent activator of NF-κB signaling. To the authors' knowledge, this is the first immunostimulatory ISD mutation described for a β-retrovirus. In human monocyte-derived dendritic cells, ISDmut increased envelope antigen expression and shifted the transcriptional program away from cellular senescence and toward antigen presentation and programmed cell death pathways, while preserving virus-like particle assembly and prefusion envelope conformation. The co-expressed GAG-ENV cassette was also shown to abrogate envelope fusion activity, a relevant parameter for the safety profile of the construct.

Human T cells recognise HERV-K-expressing lung cancer cells

Dendritic cells transduced with adenoviral vectors encoding HERV-K-ISDmut expanded both CD4⁺ and CD8⁺ T cells from healthy human donors. In an HLA-matched setting, the expanded CD8⁺ T cells recognised the non-small cell lung cancer (NSCLC) cell line HCC827, with the response partially reversed by HLA class I blockade — direct evidence that the human T cell repertoire contains cells capable of targeting HERV-K on tumor cells. This observation is of particular relevance to HERVolution's planned first-in-human study in NSCLC.

In vivo, adenoviral and mRNA-LNP vectors encoding HERV-K-ISDmut elicited strong T cell and antibody responses in mice and broke tolerance in HERV-K transgenic animals. In an exploratory study in cynomolgus macaques, immunization raised HERV-K-specific antibodies capable of binding the envelope surface unit. In a murine metastatic renal carcinoma model expressing HERV-K, prime-boost immunization significantly improved clearance of lung metastases and overall survival relative to control, and benefitted from combination with anti-PD-1 therapy.

HERV-K enters the clinic as a vaccine target

The publication comes as HERV-K is gaining acceptance as a clinically actionable antigen. In January 2026 the U.S. Food and Drug Administration cleared an Investigational New Drug application for a third-party self-amplifying RNA cancer vaccine encoding the HERV-K envelope protein, and the first patient was dosed in July 2026 in a Phase 1 study in triple-negative breast cancer. That a HERV-K envelope-directed immunotherapy has been permitted to proceed into human dosing supports the regulatory acceptability of HERV-K as a target class. HERVolution's approach is differentiated by its rationally engineered ISDmut antigen, which is designed to overcome the immune tolerance that has historically limited responses to native HERV-K sequences, and by its application across oncology, metabolic disease and cellular senescence.

"This publication is the scientific foundation of our company. It establishes that HERV-K is expressed across the vast majority of cancers, that it can be rationally re-engineered to break immune tolerance, and that the resulting immune response reaches human tumor cells. Taken together with our soon to be published data in metabolic disease and senescence, it reinforces our conviction that the dark genome is a therapeutically actionable target class — and it underpins the advance of IPT-001 toward the clinic." — J. Robert Coleman, PhD, MBA, Chief Executive Officer, HERVolution Therapeutics

"What this work shows is that a rationally chosen immunostimulatory mutation in a vector encoded and tumor antigen derived virus-like-particle is sufficient to reprogram how human dendritic cells handle antigen. This modification provides improved stimulation of CD4+ and CD8+ T cells as well as tolerance breaking B cell responses. Expansion of human T cells able to recognize HLA-matched tumor cells and animal cancer models provide translational data. This is the breakthrough the field has been searching after for decades - a available and targeted tumor antigen to make immunotherapy broadly effective and scalable" — Peter Johannes Holst, MD, PhD, Chief Scientific Officer and Founder, HERVolution Therapeutics, and senior author of the study

The study was conducted by HERVolution Therapeutics in collaboration with the University of Copenhagen, Copenhagen University Hospital – Rigshospitalet, Herlev Hospital, IPB University (Bogor, Indonesia), and Revvity Gene Delivery GmbH. It was supported by HERVolution Therapeutics together with funding from the Serum Institute of India, the European Innovation Council (EIC) Accelerator, the EUREKA Eurostars Programme co-funded by the European Union, and Innovation Fund Denmark.

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, IPT-001, is advancing toward first-in-human studies in oncology and metabolic disease. For more information, please visit hervolutiontx.com. Follow us on LinkedIn.

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