Team:Arizona State

From 2013.igem.org

Revision as of 00:59, 28 September 2013

Overview

Cancer globally kills eight million people each year, a number unchanged over the past five decades. The current paradigm for cancer treatment involves non-specific therapies such as chemotherapy and radiation that cannot differentiate between cancerous and healthy tissue. Scientists in the rising field of cancer immunotherapy are applying bionanomedical techniques to harness the patient’s own immune system to fight cancer. During primary tumor development, a patient’s innate immune function is active. However, tumors have developed a multitude of immune system inhibitors, which suppress a patient’s immune system and promote complete tumor development. We propose a novel vaccine delivery system (BactoVax) of tumor associated antigens and immunomodular agents encapsulated within probiotic bacteria, akin to those found in commercial yogurt. The proposed vaccine should breach the immunological barrier posed by primary tumors through the activation of macrophages and dendritic cells (DCs) in order to teach a patient’s immune system to recognize cell surface antigens and markers that distinguish tumors from healthy tissue. This process of “training” the immune system to target cancer stems from the adaptive immune function, which exploits the molecular properties of cytotoxic T lymphocytes, specifically the intrinsic ability to recognize tumor-associated antigens and destroy the tumor cells through induced apoptosis.

Vaccine Design

We aim to engineer the E. coli strain Nissle 1917, a probiotic already sold commercially and used as a gastrointestinal therapeutic, to train the human immune system to target and destroy tumor cells. This provides a distinct advantage over current bacterial immunotherapy methods, which rely on pathogenic strains of bacteria such as Salmonella and Listeria. The modular nature of our system allows the bacteria to train the body’s immune system to target pathogenic bacteria and viruses in addition to cancer as well as produce a variety of immunomodular agents to stimulate the immune system.

While in the body, our bacterial vaccine system secretes a stimulating factor protein that attracts dendritic cells, a type of immune antigen-presenting cell, to its location. The vaccine is engineered to target a receptor on human dendritic cells, which approach and then engulf the bacteria. Once inside, the bacteria express cancer cell markers, which the dendritic cell presents on its surface similarly to the way that current protein-based vaccines function. Cytotoxic T-cells, another type of immune cell that targets and kills mutated or cancer cells, will then recognize the cancer marker displayed on the surface of the dendritic cell and subsequently be “trained” to recognize and attack cancer cells that grow in the body. See our Data Page to view the uptake process.