Title

Creating a model antigen system to test the mechanism of GCC-specific tolerance

Authors

Patrick Ihejirika, Lincoln UniversityFollow

Document Type

Presentation

Publication Date

8-2012

Comments

Paper is attached at bottom of page.

Abstract

Immunotherapeutics for colorectal cancer have been under investigation for decades. Unfortunately, a recent meta-analysis has revealed only a 1% response rate for all immunotherapeutic trials in colorectal cancer, highlighting the need for improved immunotherapeutic target antigens which are tumor-specific, immunogenic, and shared by patients. However, to produce immunological responses targeting tumor/self antigens, one has to overcome tolerance, which has constituted an obstacle to previous studies. Guanylyl cylcase C is the index cancer-mucosa antigen, an emerging class of tumor antigens in colorectal cancer. As a mucosa-restricted antigen, GCC is amenable to immunological targeting and uniquely suited for immunotherapy of colorectal cancers. GCC is only expressed in the intestine and it is so highly restricted in its expression that it can be utilized to detect metastases in non-intestinal tissues. However, previous studies have defined tolerance as a key mechanism limiting efficacy of GCC-targeted vaccines. A tissue-specific model-self antigen expressed in the intestine is required to define tolerance mechanisms to intestinal antigens. Here, we created a model self-antigen comprised of the OT-II CD4+ T cell epitope, OT-I CD8+ T cell epitope, and HA tag B cell epitope that can be employed to create transgenic mice for studying mechanisms of GCC-specific tolerance.

22 PowerPoint slides.

Recommended Citation

Ihejirika, Patrick, "Creating a model antigen system to test the mechanism of GCC-specific tolerance" (2012). Summer Training Program in Cancer Immunotherapy. Presentation 4.
https://jdc.jefferson.edu/summercancerimmunotherapy/4