Leveraging antibody responses against transposable elements as a novel immune therapy for ovarian cancer

Principal Investigator

Name
Rebecca Lynch

Degrees
PhD

Institution
The George Washington University School of Medicine and Health Sciences

Position Title
Associate Professor

Email
rmlynch@gwu.edu

About this CDAS Project

Study
PLCO (Learn more about this study)

Project ID
2026-0096

Initial CDAS Request Approval
Jun 17, 2026

Title
Leveraging antibody responses against transposable elements as a novel immune therapy for ovarian cancer

Summary
Ovarian cancer (OC) is the fifth deadliest cancer in women, but overall survival has not significantly changed for decades and novel therapies are urgently needed for this disease. OC is characterized by an immunosuppressive tumor microenvironment1. While better prognosis is associated with higher tumor-infiltrating T and B cells, fewer than 10% of patients respond to current immune checkpoint blockade therapies2,3. The Chiappinelli lab has shown that transcription of transposable elements (TEs), which make up half of our genome, can reverse immune evasion in OC. Additionally, Curative immunotherapy (anti-CTLA-4 plus anti-PD-1) induces strong antibody responses in syngeneic murine models of melanoma, colon, and lung cancer, and sera from these cured mice can protect naïve mice against injection with other murine tumor cell lines 4,5. Interestingly, the dominant antibodies from the curative sera recognize an endogenous retrovirus (ERV) envelope glycoprotein. Our goal is to define the immune response to transposable element derived antigens that may aid in anti-tumor immunity.

Aims

Aim 1. Define the antibody response to HERV-derived antigens in ovarian cancer patients
We will quantify IgG responses against HERV-K, ERV-3, Syncytin-1 (ERV-W), and ORF1 in purified IgG from sera from ovarian cancer patients and matched healthy controls. We hypothesize that antibody responses to these antigens are elevated in ovarian cancer cohorts. To accomplish this aim, we need matched control samples to compare to our ovarian cancer cohort.
Aim 2. Identifying ERV-specific B cells and characterizing their BCRs as monoclonal antibodies. Methods: Single cell sorting B cells and cloning monoclonal antibodies.
Aim 3. Characterize the binding specificity and tumor recognition capacity of HERV-targeting monoclonal antibodies.
We will characterize the binding and specificity of isolated monoclonal antibodies using binding assays. We hypothesize that these antibodies will recognize ovarian cancer expressing HERV-derived proteins.

Collaborators

Rebecca Lynch (The George Washington University School of Medicine and Health Sciences)
Katherine Chiappinelli (The George Washington University School of Medicine & Health Sciences)