# Targeting EGFL6 in Ovarian Cancer

> **NIH NIH P50** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $204,372

## Abstract

Project 3 SUMMARY/ABSTRACT
High-grade serous ovarian cancer (HGSC) is the most common and aggressive type of epithelial ovarian cancer,
and the mortality rates remain unacceptably high. It is well documented that aberrant angiogenesis occurs in the
tumor microenvironment (TME) and angiogenesis inhibitors are important for cancer therapy. However, the
clinical benefit of bevacizumab (vascular endothelial growth factor (VEGF) targeted antibody) has been limited
due to rapid emergence of resistance in most patients with ovarian cancer. Moreover, therapies targeting the
VEGF signaling pathway can also result in adverse events and interfere with wound healing since VEGF is
known to be also important for physiological angiogenesis. Thus, new targets and approaches aimed at the TME
for improving therapeutic outcomes are needed. We identified epidermal growth factor (EGF)-like domain
multiple 6 (EGFL6) as the most differentially expressed gene in tumor endothelial cells compared to endothelial
cells from normal ovarian tissues and healing wounds. Our preliminary data suggest that high EGFL6 expression
in tumors is associated with an immune suppressive TME with high M2 macrophage infiltration. To develop a
therapeutic approach for blocking EGFL6, we developed and tested a large number of candidate antibodies; the
final candidates have been humanized. Our in vivo results indicated that these antibodies had robust anti-tumor
effects and reduced angiogenesis in ovarian cancer models. Based on our compelling preliminary data, we
hypothesize that EGFL6 promotes aberrant angiogenesis, and immune suppression, resulting in ovarian cancer
growth and progression. Blocking EGFL6 with a monoclonal antibody provides a novel and effective approach
for treatment of ovarian cancer. We will test our hypothesis under three Aims: 1) To delineate the molecular
regulation of EGFL6 and identify sources of EGFL6 in the tumor microenvironment; 2) To investigate the
biological effects of anti-EGFL6 monoclonal antibody as monotherapy or in combination with chemotherapy, anti-
VEGF antibody, or immune checkpoint inhibitor; and 3) To determine the safety and tolerability of an anti-EGFL6
antibody in a first-in-human, first-in-class phase I clinical trial in patients with recurrent ovarian cancer.
Collectively, the work proposed in this project will provide scientific rationale for developing new anti-EGFL6
based therapies. The proposed studies will provide fundamental mechanistic insights into the role of EGFL6 in
regulating immune responses in the TME. Findings from this proposal could significantly impact the clinical
outcomes of patients with ovarian cancer.

## Key facts

- **NIH application ID:** 11171048
- **Project number:** 3P50CA281701-02S2
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** ANIL K SOOD
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $204,372
- **Award type:** 3
- **Project period:** 2023-09-19 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11171048

## Citation

> US National Institutes of Health, RePORTER application 11171048, Targeting EGFL6 in Ovarian Cancer (3P50CA281701-02S2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11171048. Licensed CC0.

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