The immune system is designed to detect and attack foreign agents that are harmful to the body to help prevent infections and protect it from cancer and other diseases. However, cancer can evade an immune response by disguising itself as normal cells or by producing signals that suppress an immune response.1
In contrast to the immune system, which encompasses the entire human body, the tumor microenvironment is the specific area where a tumor exists. The tumor microenvironment consists of cancer cells, support cells (antigen presenting cells or APCs including dendritic cells), immune cells (T cells, B cells, natural killer (NK) cells and antibodies), surrounding blood and lymph vessels, and the extracellular matrix. The different types of cells constantly interact and communicate. When tumors initially form, the body’s immune system recruits and activates a host of immune cells to fight the invading tumor. However, in cases where cancer progresses, the cancer cells send out signals that promote tumor growth and suppress an immune response.
Effective immunotherapy is designed to override the tumor defense mechanisms within the tumor microenvironment by activating both innate and adaptive arms of the immune system.
Innate immunity comprises cells and chemicals naturally present within the immune system which mount an immediate and general defense. The innate immune system includes physical barriers like the skin, natural killer cells that attack foreign invaders and cytokines that signal more specific immune cells to move to the site of invasion. The innate immune system mounts its response immediately, within hours or days.
Concurrently, antigen presenting cells (APCs), including dendritic cells (DCs), activate and recruit the adaptive immune response to react specifically to the threat. The adaptive immune response is highly specialized and responds by directly attacking and eliminating the cancer or pathogen, and at the same time protect the body against future invasions. Specifically, antigen presenting cells (APCs) signal specific T cells to proliferate, creating an army of T cells designed to attack that particular threat. Once the cancer or pathogen is eliminated from the body, these T cells remain and circulate throughout the body, protecting it from future similar attacks.
Aduro’s immunotherapies are uniquely designed and differentiated to stimulate both innate and adaptive immunity to combat different types of cancer.
The image below explains how the immune response is generated against the tumor:
Aduro’s technologies are designed to boost the immune response as illustrated above:
- LADD® is designed to boost T cells against a specific antigen expressed by the tumor cells (e.g. mesothelin) to initiate an immune response as well as to induce innate immunity
- STING pathway activators are designed to activate antigen presenting cells within the tumor microenvironment, thus inducing the generation of specific T cells against certain antigens which are particular to each patient’s tumor
- B-select monoclonal antibodies are designed to inhibit checkpoint signaling or activate immune stimulators
Due to the complexity of the immune response, Aduro believes that the future of successful treatment will be derived by combining immunotherapies that target different phases of the immune cycle.
Aduro’s immunotherapy agents may also be beneficial in treating infectious diseases through immune activation and autoimmune diseases through immune modulation.
1 National Cancer Institute. Website accessed February 25, 2016: http://www.cancer.gov/research/areas/treatment/immunotherapy-using-immune-system