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

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. ...
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