Description:
Human epidermal growth factor (EGF)-like domain multiple 6 (EGFL6) was discovered in tumors and fetal tissues. Upregulated expression of EGFL6 was found in a variety of cancer cell types, such as ovarian cancer and lung cancer. Unlike VEGF, which was expressed in ovarian cancer tissues and in healing wounds, EGFL6 was expressed mainly in tumor-associated endothelial cells. UTHealth researchers and collaborators created humanized EGFL6-targeted antibodies and demonstrated that anti-EGFL6 antibodies blocked tumor angiogenesis but did not affect normal wound healing. Thus, the novel anti-EGFL6 antibodies provide possible new effective methods for treating cancers and inhibiting angiogenesis.
Background
Angiogenesis is a key target in cancer therapy. To date, multiple anti-angiogenesis drugs, such as bevacizumab against VEGF, have been developed and tested. However, current angiogenesis inhibitors, such as bevacizumab, can cause intolerable adverse effects, including bleeding and impaired wound healing. Therefore, identifying unique targets that have differential expression between normal and tumor angiogenesis could be highly valuable. Identifying inhibitors against those unique tumor-specific targets can further improve the efficacy and safety of anti‐angiogenesis therapeutic approaches.
Significance and Impact
UTHealth researchers and collaborators demonstrated that, while VEGF was expressed in ovarian cancer tissues and in healing wounds, EGFL6 was expressed mainly in tumor-associated endothelial cells. They analyzed the EGFL6 target and generated high affinity, monoclonal EGFL6-targeted antibodies from rabbit B cells after immunization with the EGFL6 antigen. With a series of in vitro and in vivo studies, the selected monoclonal EGFL6 antibodies exhibited an effective blocking effect in tumor angiogenesis but did not affect normal wound healing.
Technology Highlights
- EGFL6 is upregulated in tumor-associated endothelial cells but has limited expression in healthy tissue.
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Anti-EGFL6 antibodies block tumor growth and angiogenesis but do not prevent wound healing in vitro and in vivo.
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Anti-EGFL6 antibodies block EGFL6-mediated functional effects on tube formation and migration.
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Tumors treated with the EGFL6-targeted antibodies showed decreased cell proliferation and microvessel density (MVD).
Potential Applications
The novel monoclonal EGFL6 antibodies can be applied to cancer diagnostics and therapeutics. The EGFL6-targeted antibodies bind effectively to EGFL6 with high affinity and block tumor angiogenesis without affecting wound healing. Compared to the effect of anti-VEGF drugs on wound healing in anti-angiogenesis therapy, EGFL6 is a more selective target and represents an attractive therapeutic target for inhibiting ovarian and other cancers while mitigating off-target effects and toxicity. The novel EGFL6 antibodies could potentially develop into antibody cancer therapies with minimal impact on wound healing.
Intellectual Property Status
Granted Patents in US, CN, SP, JP, ID, ZA, and RU.
Patents filed in EU, KR, CA, HK, AU, BR, MX, NZ, IN
Available for licensing
Related Publication
Noh et al. Cell Reports 21, 2785-2795. (2017)
An et al. Oncogene 38, 2123-2134. (2019)
About the Inventor
Zhiqiang An, Ph.D.
Vice President of Drug Discovery at UTHealth Houston
Dr. An is a world leader in therapeutic biologic drugs. Researchers in Dr. An's lab are working on innovative treatments for cancer and other human diseases, especially targeted treatments involving the use of engineered antibodies.
Ningyan Zhang, Ph.D.
Professor at UTHealth Houston, Co-Director of the Antibody Drug Discovery Lab at McGovern Medical School, and Co-Director of the CPRIT Therapeutic Antibody Core.
Dr. Zhang is working on translational research with a focus on evaluation of new cancer targets and development of platform technologies for therapeutic antibody discovery.
Anil K. Sood, M.D.
Professor and Vice Chair for Translational Research in the Departments of Gynecologic Oncology and Cancer Biology and co-director of the Center for RNA Interference and Non-Coding RNA at the MD Anderson Cancer Center
UTHealth Ref. No: 2015-0059