SUMMARY A diagnosis of ovarian cancer (OvCa) is especially devastating. With 22,240 diagnoses in 2018 and an estimated 14,070 deaths, OvCa has the third-highest mortality rate, leading to the fifth-highest number of cancer deaths among women in the United States. The objective of this research is to validate the anti-tumor function of humanized antibodies with the end goal of identifying and developing an optimized lead monoclonal antibody (mAb) as a therapeutic antibody against Epidermal Growth Factor-Like 6 (EGFL6), a mediator of tumor growth and metastasis. Our first indication for treatment with the therapeutic antibody will be patients with platinum resistant ovarian cancer (OvCa), post-PARP (poly-ADP ribose polymerase) inhibitor treatment, which is a growing area of need. Our proposed therapeutic neutralizes EGFL6 by disrupting its functions to promote cancer cell growth, act as a chemotactic factor in the tumor microenvironment to promote metastasis, and promote angiogenesis. The proposed Phase I research objectives are focused on identifying the antibody most efficacious in inhibiting tumor growth and metastasis for further characterization and development as a therapeutic antibody. Upon successful completion of this Phase I study, the next steps in Phase II will include evaluating toxicity alone as well as efficacy in combination with other OvCa therapeutics in order to address regulatory requirements and refine concepts for clinical trials.