Immunotherapy Targeting Stromal CD5L in Ovarian Cancer
Abstract
Although the FDA approved anti-angiogenesis therapies, such as bevacizumab, for treatment in upfrontand relapsed ovarian cancers, the development of adaptive resistance to such therapy remains a majorclinical barrier. To date, only a portion of the molecular mechanisms underlying drug resistance to antiVEGF antibody therapy like bevacizumab have been studied. The proposed work aims to investigate thetherapeutic potential for a novel monoclonal antibody, rAb-anti-CD5L to overcome adaptive resistance inovarian cancer during application of anti-VEGF drugs. We also aim to characterize the roles for CD5L andits endothelial-specific receptors in mediating development of resistance to anti-VEGF antibodytherapeutics in endothelial cells, and the mechanisms of rAb-anti-CD5L in interfering with such activities.The short-term goal of this proposal is to understand mechanisms of action of rAb-anti-CD5L in targetingstromal CD5L in ovarian tumors with anti-VEGF-therapy resistance. We expect this work will lead to a newtherapeutic approach for ovarian cancer patients. Overall, our proposal is highly translational and hasprofound implications for developing a novel, antibody-based therapy for ovarian cancer. Thus, thisproposal is directly responsive to the Program Announcement for the Investigator-Initiated Research Awardfrom DOD-OCRP, in that we will identify novel approaches for overcoming adaptive resistance to antiVEGF therapy in ovarian cancer. Further clinical development of rAb-anti-CD5L will require formal safetystudies (GLP regulations); we are well poised to carry out such work and have extensive experience indrug development. As the future effort, we will take advantage of the Moonshot Program for Ovarian Cancerat MD Anderson, which will provide clinical resources for us to formally test the utility of anti-CD5L antibodybased drugs to overcome the adaptive resistance developed from anti-angiogenic therapy includingbevacizumab.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1218020
Entities
People
- Yunfei Wen
Organizations
- The University of Texas MD Anderson Cancer Center