Targeting a powerful immune response in the liver is key.

The last ten years has seen significant advances in the field of immunotherapy and it is now recognised by researchers, clinicians, industry and regulators as an essential modality to treat many diseases. It offers significant advantages over other therapies by reducing side effects, overcoming immune tolerance and offering greater specificity to achieve long lasting results for patients.

Innate and adaptive immunity–

Innate immunity provides the early line of defence against foreign substances, such as a virus, microorganism or cancer cells, using a number of physical and chemical barriers and inbuilt immunity to rapidly respond to infections or cancer.

Adaptive immunity is often referred to as specific or acquired, meaning it has the ability to distinguish between different foreign substances and respond more vigorously to repeated exposure.  This is also known as a memory response. Foreign substances that induce specific immune responses or are recognised by your immune system are called antigens.

Avalia’s immune therapies are designed with specific antigens in mind. Our clever design incorporates a synthetic version of the target antigen with novel agonists to stimulate a potent and specific immune response against the chosen target.

Our novel agonists, are innate-like T cell agonists, that specifically target and stimulate a special family of immune cells called natural killer T (NKT) cells.  NKT cells are primarily located in the liver and spleen and once stimulated, are primed to interact with professional antigen-presenting cells (APCs), such as dendritic cells or DCs, to greatly improve their function. This process is highly efficient causing the APCs to drive the expansion of large populations of antigen (disease)-targeted cytotoxic T cells.

Our own studies have shown that dendritic cells (DC) - the most effective APCs in the body - can be licensed by NKT cells to drive particularly powerful T cell responses in the absence of any other signals, providing an opportunity to use NKT cell agonists in immunotherapy development.

Immune modulators that target the liver–

Avalia’s immune modulators (and vaccines) incorporate two key components; a natural killer T (NKT) cell agonist and an antigen, which are covalently attached to drive a powerful and robust immune response.

These immune system modulators are discrete chemical entities containing synthetic long peptide antigens that represent sequences from the target antigens. They are covalently linked using an enzymatically cleavable linker to a modified NKT cell agonist, and in our design this is specifically modified alpha-galactoceramide (or a-GalCer). Once these synthetic structures reach professional antigen presenting cells, the linker  is cleaved by intracellular enzymes, resulting in the release of the active components; the antigen and the NKT cell agonist.

The NKT cell agonist is then presented by dendritic cells in a manner that attracts powerful stimuli from NKT cells, while the antigen is simultaneously presented to T cells. Having received signals from the NKT cells, the dendritic cell stimulates proliferation of T cells that recognise the presented antigen. These T cells undergo clonal proliferation, and gain the ability to circulate the body and eradicate infected tissues or tumors that express the same antigen.

Our proprietary chemical design drives particularly powerful T cell responses in the absence of any other signals and also generates liver tissue resident memory T cells (liver Trms) in significantly high numbers.