Breakthrough Technology   Why Gene Transfer is Promising We believe gene transfer is a promising approach for treating cancer. Unlike current conventional cancer treatment of cytotoxic chemotherapy and radiation therapy, gene transfer has the potential to deliver a therapeutic gene directly to cancer cells.  The therapeutic genes serve as the instructions for producing therapeutic proteins that are designed to kill the cancer cells directly, or to activate immune cells which then kill the cancer cells. We believe gene transfer has the potential to be highly effective, with fewer side effects compared to conventional cancer treatment.    Tocagen believes its proprietary gene transfer technology represents an important improvement over prior gene transfer approaches.  Initially, researchers used non-replicating viruses which lacked the ability to transfer the therapeutic gene throughout the entire cancer.  More recently other researchers have evaluated replicating viruses which lyse infected cells (oncolytic viruses), but whose spread and therapeutic effect are limited by the patient's immune response against the virus. We believe Tocagen's technology platform has overcome the problem of not being able to transfer the gene throughout the entire cancer and now may be able to fulfill the promise of gene transfer as a treatment for cancer. Our Breakthrough CAGT Technology Our Controlled Active Gene Transfer Technology (CAGT) platform is a unique gene transfer technology that uses a non-oncolytic, replicating virus. Based on experiments in mice, our virus is cleared from healthy cells by the immune system.  However, our virus is not cleared from the cancer cells by the immune system allowing delivery of the therapeutic gene to the entire cancer. Tocagen's gene transfer approach is designed to enable the therapeutic gene to selectively destroy cancer cells while not harming healthy tissue.   We believe the ability of our virus to selectively deliver the therapeutic gene to cancer cells results from multiple mechanisms. Our CAGT virus only grows in dividing cells such as cancer cells. Also, our virus is controlled by the immune system (including intracellular immunity) in healthy cells, but is not cleared in cancer tissue by the immune system.  The cancer tissue has mechanisms to evade the immune system, which allows the virus to also persist.  In brain cancer (glioblastoma multiforme) studies performed in mice and rats with a competent immune system, the CAGT virus spread through the brain cancer and resulted in marked cancer regression, while not harming healthy tissue. Recent Advances Pave the Way Over the past two decades significant advances have been made in gene transfer technology such as vector (gene delivery vehicle) construction, vector producer cell efficiency and scale-up processes, preclinical models for target diseases and regulatory guidance regarding clinical trial design including endpoint definitions and measurements. Thus many aspects of gene transfer technology have matured to the point of clinical and commercial feasibility. CAGT Technology Potential Advantages Treatments developed with our CAGT gene transfer technology are designed to be more effective than previous gene transfer technologies used in cancer.  Tocagen's product candidates selectively target cancer tissue for viral spread and gene delivery, allowing for localized treatment effects without the side effects normally seen with less targeted treatments.  Based on multiple preclinical animal studies in numerous types of cancer, we believe that our CAGT technology is a platform that may be used for the development of treatments for multiple cancer types.   Programs  Brain Cancer (GBM)  Malignant Melanoma   Product Candidates  Prodrug Activator: Toca 511  Immunotherapeutic: Toca 621                                               Dictionary     Dictionary of Cancer Terms       Privacy Policy | Terms of Use | www.tocagen.com   3030 Bunker Hill St. Suite 230  San Diego, CA 92109          Main (858) 412-8400  Fax (858) 412-8499  © Copyright 2010 Tocagen Inc.