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Novel Human Immunogenic Epitopes of the Human Endogenous Retrovirus ERVMER34-1

Summary
Researchers at the NCI developed immunologically active peptides of the human endogenous retrovirus ERVMER34-1 that bind to human leukocyte antigen A2 (HLA-A2) and elicit multifunctional T cell responses in cancer patients. These peptides and associated agonist epitopes can be used to develop cancer vaccines for the prevention and/or treatment of several cancer types. NCI seeks licensees or co-development partners to commercialize this invention.
NIH Reference Number
E-159-2019
Product Type
Keywords
  • Human endogenous retroviruses, HERV, human leukocyte antigen A2, HLA-A2, Peptides, Cancer, T cells, Vaccines, Peripheral blood mononuclear cells, PBMCs, Immunogenicity, Schlom.
Collaboration Opportunity
This invention is available for licensing and co-development.
Description of Technology

Human endogenous retroviruses (HERV) are an ongoing area of research for targeted cancer therapy. HERVs are relics of ancient retroviral infection of the germ line which occurred early in primate evolution. They make up about 8% of the human genome. It is now known that HERV RNAs and/or proteins are overexpressed in a range of human tumors compared to normal tissues – despite most HERV components being nonfunctional due to epigenetic control or deactivating mutations,. 

Cancer patients have T cells reactive with specific HERV peptides. Human T cells generated in vitro by employing specific HERV peptides were observed to lyse tumor cells in breast cancer and melanoma models. These T cells were also found to inhibit metastasis development in the liver, brain, lungs, and lymph nodes in mouse xenograft models. Therefore, HERV peptides might serve as tumor-associated antigens. Vaccines developed against such antigens offers new treatment and/or prevention opportunities for diverse types of cancer without eliciting an autoimmune response. 

The investigators at the NCI identified novel native and agonist peptides of ERVMER34-1 that bind to HLA-A2 and HLA-A24. Theses epitopes were not described previously and are different from other HERV peptides. Peripheral blood mononuclear cells (PBMCs) from colorectal, appendiceal, and bladder cancer patients show T-cell responses to these peptides. Several of these T cells are highly functional with high lytic potential against tumor cells. These results suggest that HERV immunogenic peptides and associated agonist epitopes can be used to develop peptide and/or vector-based vaccines and/or develop combination therapies with non-HERV vaccines against various cancers.

The NCI seeks licensees or co-development partners to commercialize this invention.

Potential Commercial Applications
  • Cellular therapy directed against ERVMER34-1 
  • Combination therapy with other non-HERV vaccines.
  • Peptide cancer vaccine.
  • Vector-based cancer vaccine.
  • Liposome-based cancer vaccine.
  • Combination therapy with other immune or non-immune-based therapies.

 

Competitive Advantages
  • Targeted therapy ameliorates non-specific killing of normal cells, potentially resulting in fewer side-effects and healthier patients.
  • Technology not restricted to tissue type.
  • Elicits multifunctional T cell response with increased lytic function.
  • Combination therapy with other non-HERV vaccines or other I-O agents.
Development Stage
Publications

1.  F. Zhou, et al. Chimeric antigen receptor T cells targeting HERV-K inhibit breast cancer and its metastasis through downregulation of Ras Oncoimmunology.

2.  J. Krishnamurthy, et al. Genetic engineering of T cells to target HERV-K, an ancient retrovirus on melanoma. 

Benjamin Kraus, et.al, Vaccination directed against the human endogenous retrovirus-K (HERV-K) gag protein slows HERV-K gag expressing cell growth in a murine model system.

Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 62/963,872, Filed 21 Jan 2020
  • PCT: PCT Application Number PCT/US2021/014335, Filed 21 Jan 2021
Therapeutic Area
Posted
Wednesday, July 6, 2022