# Combining repetitive element-specific T cells with epigenetic therapy to treat ovarian cancer

> **NIH NIH F31** · GEORGE WASHINGTON UNIVERSITY · 2022 · $40,877

## Abstract

The five year survival rate for ovarian cancer (OC) patients has remained at 47% for over two decades.
OC is characterized by a highly suppressive tumor microenvironment and current research efforts focus on
reversing this immune suppression. One way to activate the immune response against OC is using epigenetic
therapeutics, which stimulate an interferon response in cancer cells by inducing the transcription of repetitive
elements (REs)—genomic regions that resemble the genetic material of some viruses. As REs are normally
silent in terminally differentiated cells, their upregulation in tumor cells suggests that these genomic elements
can be used as inducible treatment targets. T cells specific for an RE-derived antigen, the non-functional
envelope gene of endogenous retrovirus K (ERV-K-Env), can recognize their cognate antigen and kill OC cells
while sparing healthy cells. Whether these T cells will be more lytic when combined with immunogenic epigenetic
therapy is unknown. Aside from ERV-K-Env, other epigenetically upregulated REs serve as an unexplored pool
of tumor-associated antigens that may be novel treatment targets. I hypothesize that combining epigenetic
therapy with RE-specific T cells will have potent immunogenic and targeted anti-tumor efficacy in OC.
 In Aim 1, I will determine the effect of combination epigenetic therapy and ERK-K-Env-specific T cells in
OC. Preliminary data suggest this candidate RE, ERV-K-Env, is a targetable tumor-associated antigen in OC. I
hypothesize that combining epigenetic therapy with ex vivo expanded ERV-K-Env-specific T cells will
result in targeted immunogenic OC cell killing. ERV-K-Env-specific T cells will be expanded ex vivo from
whole blood donors and assessed in vitro for antigen specificity. I will co-culture the expanded T cells with
epigenetically treated OC cells and assess T cell activation and cytotoxicity in vitro and in vivo.
 In Aim 2, I will identify and target additional tumor-associated RE peptides as novel OC tumor antigens.
Preliminary data from my lab suggest that epigenetic treatment results in the upregulation of REs and their
presentation on the surface of OC cells to the immune system. I hypothesize that diverse tumor-associated
REs upregulated by epigenetic therapy can be therapeutically relevant T cell targets in OC. Bioinformatic
tools will be used to identify which REs upregulated by epigenetic therapy have the potential to be T cell antigens.
I will validate the immunogenicity of these antigens by expanding RE-specific T cells from healthy donors and
assess the clinical relevance of the experimentally validated REs as treatment targets using OC patient T cells.
 Completion of the proposed project will provide new knowledge on the combination of epigenetic therapy
with RE-specific T cells as a novel immunogenic and potentially curative treatment strategy for OC. Collectively,
these innovative interdisciplinary experiments will shed light on the understudied role of REs as t...

## Key facts

- **NIH application ID:** 10465402
- **Project number:** 1F31CA271788-01
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Erin Elizabeth Grundy
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $40,877
- **Award type:** 1
- **Project period:** 2022-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465402

## Citation

> US National Institutes of Health, RePORTER application 10465402, Combining repetitive element-specific T cells with epigenetic therapy to treat ovarian cancer (1F31CA271788-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10465402. Licensed CC0.

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