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Colorectal cancer is the second leading cause of cancer-related death in US (1). Most of the mortality reflects local, regional and distant metastatic tumors. Cancers that are confined within the wall of the colon are often curable with surgery while tumor cells that have spread into other organs like liver and lung has low curable possibility, even though the chemotherapies and monoclonal antibodies can extend the person's life and improve quality of life(2, 3). Surgery is the main treatment for primary colorectal tumors but recurrence can happen and develop into metastasis. In addition, colorectal cancer has been proved resistant to chemotherapy although little success has been achieved using a combination of 5-fluorouracil and levamisole. Survival rate decreases from 90% for primary tumors to 10% for distal metastasis of colorectal cancer (1). More attention has been attracted to immunotherapy against metastatic colon cancer, because of its potential for higher specificity and less side effect(4). Our main aim is to increase the eradication of metastatic colorectal cancer cells by optimizing immunotherapeutic approaches that have been well-underway. Guanylyl cyclase C (GCC) is a mucosal antigen expressed on apical surface of intestinal epithelial cells. It is a potential target for colorectal cancer immunotherapeutic approaches, because of its expression on >95% of colorectal cancer cells and their maintenance through all the stages of colorectal cancer (5-9).This is because GCC is mainly expressed in the intestine so that its expression can be utilized to detect metastasis of colon cancer. The aim of this project is to develop an immunotherapy based on GCC-specific TCR transduced CD8 T cells to attack metastatic cancer cells. The initial step of this project is cloning out CD8 TCR specific to GCC. This can be done by T-hybridoma technology by which we fused T cells from mice immunized by GCC vaccine with fusion partner cells (BWZ/CD8)(10).

Paper on Adoptive T Cell Therapy for Metastatic Colorectal Cancer.pdf (548 kB)
Paper on Adoptive T Cell Therapy for Metastatic Colorectal Cancer

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