Aduro has three interconnected and complementary vaccine platforms. These platforms give us breadth and depth in developing vaccines for cancer, infectious diseases and biodefense. Moreover, the combinatorial capabilities, including the regimen in our Phase 2 clinical trial, give us a leading position in the rapidly-emerging use of combination therapies.
1. Live, attenuated Listeria monocytogenes: For more than 50 years, immunologists have used Listeria as a research tool to study the mammalian immune system. Now Aduro is engineering Listeria to treat cancer and infectious diseases. Using Listeria in this way may seem counter-intuitive, but our platform has shown to be well tolerated in multiple clinical trials.
Listeria has multiple advantages as a vaccine platform:
(a) It directly targets dendritic cells, one of the most important types of cells in initiating an immune response.
(b) After being taken up by dendritic cells, Listeria delivers the disease antigen(s) into the cytosol where they are processed by the host cellular machinery and presented to the immune system.
(c) Listeria signals to the innate immune system through multiple pathways, activating cell surface Toll-like receptors and intracellular Nod-like receptors.
(d) Unlike other vaccine vectors that can be neutralized by antibodies, Listeria can be repeatedly administered.
(e) Listeria is exceptional at boosting the efficacy of other vaccines/treatments.
(f) Listeria is self-replicating and easy to manufacture.
2. GVAX. GVAX is a
portfolio of vaccines based on tumor cell lines from specific types of
tumors that have been engineered to recruit dendritic cells by
expressing GM-CSF. Aduro has extensive preclinical data and anecdotal
human clinical data indicating that the combination of GVAX
and Listeria is synergistic, which led to the design of our ongoing Phase 2
trial. Furthermore, we have also shown that GVAX is potentiated by the
addition of CDNs (see below), which are potent dendritic cell activators.
3. Cyclic Dinucleotides (CDNs). CDNs are small molecules secreted by Listeria and other intracellular pathogens that signal through STING (STimulator of INterferon Genes) and induce a potent immune response. The biology of CDNs and STING is currently an area of great excitement, and the field is rapidly developing. Aduro currently has a strong proprietary position through strategic licensing of key intellectual property and through our development efforts integrating a synthetic chemistry group to make new derivatives with a dedicated immunology team to evaluate the derivatives. We are making progress towards a Phase 1 clinical trial combining CDNs and GVAX into a second-generation vaccine platform known as STINGVAX (also see above).