The National Cancer Institute (NCI) seeks research co-development partners and/or licensees for the clinical translation of novel peptide-based therapeutic cancer vaccines derived from ERVMER34-1, a human endogenous retrovirus (HERV) antigen, offering a unique opportunity to address a significant unmet need in the treatment of various carcinomas.
Human Endogenous Retroviruses (HERVs), remnants of ancient retroviral germline infections that comprise ~8% of the human genome, represent a promising yet underexplored frontier in targeted cancer therapy. Although typically epigenetically silenced in normal adult tissues, select HERV components, including RNAs and envelope proteins, are frequently overexpressed in various carcinomas due to epigenetic dysregulation – a hallmark of cancer. The challenge lies in identifying specific, highly immunogenic HERV targets that elicit potent anti-tumor immune responses without triggering autoimmunity. Addressing this need is critical to advancing broadly applicable cancer immunotherapies.
Inventors at the NCI have developed and characterized a novel cancer immunotherapy platform targeting ERVMER34-1, a specific HERV envelope protein that is highly expressed across multiple human carcinomas while exhibiting minimal expression in normal tissues. Using transcriptomic and proteomic datasets, the team confirmed the tumor-selective expression profile of ERVMER34-1. To improve safety and specificity, they engineered an artificial antigen-presenting cell line to express the full-length ERVMER34-1 protein, HLA-A2 and CD80 to facilitate efficient priming and expansion of ERVMER34-1-reactive CD8+ T cells. To therapeutically target ERVMER34-1, they modified the ERVMER34-1 protein by removing the signal peptide, cleavage site, predicted immunosuppressive domain, transmembrane domain and a 170-amino acid region homologous to human proteins. These modifications prevent surface trafficking, antigen shedding, immune dampening, and off-target reactivity. This modified sequence was incorporated into a recombinant adenoviral vector as a therapeutic cancer vaccine. In preclinical murine models (e.g., MC38 colon cancer, EMT6 breast cancer), vaccination with this construct alone or in combination with immune checkpoint blockade or an IL-15 superagonist elicited robust, multifunctional CD4⁺ and CD8⁺ T cell responses. Those enhanced T cell responses induced tumor clearance, increased intratumoral lymphocyte infiltration, broadened neoantigen spreading and prolonged tumor control. ERVMER34-1-reactive T cells could be expanded from both healthy donor and cancer patient Peripheral Blood Mononuclear Cells (PBMCs) and demonstrated specific cytolytic activity against ERVMER34-1⁺ human carcinoma cell lines in vitro. To support peptide-based approaches, researchers developed an overlapping 15-mer peptide library spanning the modified ERVMER34-1 protein sequence. These peptides elicited strong, polyfunctional T cell responses in vitro – including both CD4⁺ and HLA-A2-restricted CD8⁺ T cell activation, enabling precise epitope mapping and facilitating future peptide vaccine design and adoptive T cell receptor (TCR)-based therapies.
The NCI invites industry partners and translational researchers to collaborate on or license this pioneering HERV ERVMER34-1 protein targeted vaccine technology. With promising preclinical data, this technology addresses a critical gap in the cancer vaccine landscape. It offers a unique opportunity to advance a novel therapeutic targeting widespread carcinomas, opening a substantial market for cancer treatment.