Characterization of Novel Vaccine Targeting Follicle-Stimulating Hormone Receptor in Ovarian Cancer
Abstract
Ovarian cancer has a high burden of disease and death. More than 50% of women diagnosed with ovarian cancer have just a 5-year survival rate. Many respond initially to traditional treatment; however, recurrence is high. Interesting post treatment there is little disease, and the tumor burden is low, presenting an important opportunity for the use of immunotherapy to improve treatment for this disease. We focused on a two-pronged approach for immunotherapy of ovarian cancer. 1) The use of active immunization to drive antibody and T cell immunity against antigens expressed specifically in ovarian disease targeting the native follicle-stimulating hormone receptor (FSHR). We developed a therapeutic vaccine for the FSHR antigen and demonstrated that it activates the immune system in mice and improves survival in animals. We have been studying the induced immune responses as per the grant in detail and observed that the novel immunogen generated novel T cell responses that are important for impacting the tumor. We are studying additional tumor specific epitopes to increase the immune effect of the vaccine and improve T cell breadth. 2) We observed that the vaccination induced antibodies that target the native FSHR structure. This was important as the FSHR antigen is a 7 transmembrane molecule which is difficult to fold in vivo limiting generation of native immune responses. We are studying this response of the humoral immune response combining the vaccine with targeted FSHR immunotherapy to provide additional impact. We have generated genetically modified antibodies as tools. In this progress update we describe development of mAb that are potent for human FSHR that were developed using the unique FSHR vaccine immunogen. This provides us with dual targeting for ovarian tumor therapy. In addition, we continue to focus on development of multivalent immunization for Ovarian cancer to complement our FSHR vaccination strategy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2022
- Accession Number
- AD1216842
Entities
People
- David Weiner
Organizations
- Wistar Institute