Antibody therapeutics for epithelial ovarian cancer

ABSTRACT

Introduction

High-grade serous ovarian carcinoma (HGSC) is an aggressive subtype of epithelial ovarian carcinoma (EOC) and remains the most lethal gynecologic cancer. A lack of effective and tolerable therapeutic options and nonspecific symptoms at presentation with advanced stage of disease are among the challenges in the management of the disease.

Areas covered

An overview of ovarian cancer, followed by a discussion of the current therapeutic regimes and challenges that arise during and after the treatment of EOC. We discuss different formats of antibody therapeutics and their usage in targeting validated targets implicated in ovarian cancer, as well as three emerging novel proteins as examples recently implicated in their contribution to adaptive resistance in ovarian cancer.

Expert opinion

Antibody therapeutics allow for a unique and effective way to target proteins implicated in cancer and other diseases, and have the potential to radically change the outcomes of patients suffering from ovarian cancer. The vast array of targets that have been implicated in ovarian cancer and yet the lack of effective therapeutic options for patients further stresses the importance of discovering novel proteins that can be targeted, as well as predictive biomarkers that can inform the stratification of patients into treatment-specific populations.

KEYWORDS:

• Adaptive resistance
• angiogenesis
• antibody therapy
• CD5L
• EGFL6
• epithelial ovarian cancer
• hypoxia
• MSMP
• ovarian cancer

Article highlights

• Ovarian cancer remains the most lethal gynecologic cancer.

• The ovarian cancer microenvironment is a complex interaction between immune and cancer cells and plays a critical role in tumor growth and adaptation.

• Immune checkpoint inhibitors have so far proved to be only minimally active against ovarian cancer.

• Resistance to anti-angiogenic therapeutics such as bevacizumab develops in most patients during or after treatment that sustains and promotes tumor vascularization and growth.

• Antibody therapeutics are an attractive therapeutic modality due to their high specificity, low off target effects, and ability to be engineered into formats such as antibody-drug conjugates, bispecific antibodies, and bispecific T-cell engaging antibodies.

• The identification of new targets that can reverse therapeutic resistance and decrease tumor growth and metastasis is urgently needed.

• Novel targets that include, CD5L, EGFL6, and MSMP have been implicated in their contribution to the progression of ovarian cancer, and preclinical data indicate that inhibition of these proteins by antibodies, RNAi, and/or aptamers can reduce tumor growth and reverse adaptive resistance in ovarian cancer.

Declaration of interests

The University of Texas System has filed patent applications on the EGFL6 and CD5L targeting antibodies, and N Zhang, AK Sood and Z An are named inventors of the patent applications. AK Sood has received research support from MTrap, is a shareholder of BioPath, and is a consultant for Merck, AstraZeneca, Onxeo, GSK, and Kiyatec for interests unrelated to the topics discussed in this paper. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was funded, in part, by The Cancer Prevention and Research Institute of Texas (CPRIT) Grants RP150551, RP190561 and Welch Foundation grant no. AU-0042-20030616, the MD Anderson Ovarian Cancer Moon Shot Program; P50CA217685, R35CA209904, P30CA016672, the Ovarian Cancer Research Alliance, the American Cancer Society, and the Frank McGraw Memorial Chair in Cancer Research.