Vaccinating against IGFBP-2 to prevent ovarian cancer relapse (Abbrev: IGFBP-2 vaccine)
The ultimate goal of this project is to conduct a Phase I clinical trial of active immunization with an IGFBP-2 Class II polyepitope plasmid DNA vaccine in patients with advanced stage ovarian cancer in the adjuvant setting.
Ovarian cancer is immunogenic, and immunity may confer a better prognosis1. If immunity could be generated in the majority of advanced stage ovarian cancer patients early in the course of their disease, perhaps clinical outcomes could be improved. A vaccine targeting immunogenic biologically relevant proteins in ovarian cancer could offer such a possibility. The development of a potentially therapeutic immune response via active immunization, a response that would result in the eradication of minimal residual disease in ovarian cancer patients, requires both an immune target that is expressed on the majority of ovarian cancers and a method of vaccination that has the potential to actively modulate the immunosuppressive factors at play in the ovarian cancer microenvironment.
We have identified insulin like growth factor binding protein 2 (IGFBP-2) as an ovarian cancer antigen. IGFBP-2 is a member of the insulin like growth factor receptor family and is a circulating protein that can be detected in the sera of ovarian cancer patients. IGFBP-2 is emerging as a potentially important regulator of ovarian cancer invasiveness and metastatic potential. IGFBP-2 is over expressed in ovarian cancers and the level of overexpression is associated with invasive disease. Immunologic eradication of tumor cells overexpressing IGFBP-2 could be beneficial in preventing disease relapse or tumor spread throughout the peritoneum.
In the course of this project we will (1) identify IGFBP-2 specific class II epitopes that bind with high avidity across multiple class II alleles and do not stimulate TGF-beta (β) production in PBMC for inclusion in a polyepitope vaccine, (2) evaluate the immunogenicity, therapeutic efficacy, and safety of an IGFBP-2 class II polyepitope plasmid DNA vaccine in a mouse model of IGFBP-2 overexpressing peritoneal metastasis, and (3) conduct a Phase I clinical trial of active immunization with an IGFBP-2 Class II polyepitope plasmid DNA vaccine in patients with advanced stage ovarian cancer in the adjuvant setting.
The inclusion and exclusion criteria are summarized in this PDF document.
For additional details on this clinical trial, please visit ClinicalTrials.gov.
Project 5 Publications
1. Cecil DL, Holt GE, Park KH, Gad E, Rastetter L, Childs J, Higgins D, Disis ML. Elimination of IL-10-Inducing T-Helper Epitopes from an IGFBP-2 Vaccine Ensures Potent Antitumor Activity. Cancer Res. 2014 Apr 28. [Epub ahead of print]. DOI: 10.1158/0008-5472.CAN-13-3286. PMID: 24778415. PubMed Link ↗
2. Disis ML, Gad E, Herendeen DR, Lai VP, Park KH, Cecil DL, O'Meara MM, Treuting PM, Lubet RA. A multiantigen vaccine targeting neu, IGFBP-2, and IGF-IR prevents tumor progression in mice with preinvasive breast disease. Cancer Prev Res (Phila). 2013 Dec;6(12):1273-82. doi: 10.1158/1940-6207.CAPR-13-0182. Epub 2013 Oct 23. PMID:24154719 PubMed Link ↗
3. Liao JB, Disis ML. Therapeutic vaccines for ovarian cancer. Gynecol Oncol. 2013 Sep;130(3):667-73. doi: 10.1016/j.ygyno.2013.06.023. Epub 2013 Jun 22. PMID:23800697 Review. PubMed Link ↗