IMMUNE ENHANCER PLATFORM

Introduction 

ABIVAX’s IMMUNE ENHANCER PLATFORM focuses on invariant natural killer (or iNKT) agonists, which have been shown to stimulate both humoral and cellular immune responses and may have clinical applications in both infectious diseases and oncology.

Immunity and Immune Enhancers 

The human immune system comprises many biological structures and complex processes within the organism to fight not only harmful pathogens but also to eliminate inadequate and/or aberrant endogenous cells including cancer cells. To function properly, the immune system must detect a wide variety of different targets, so called antigens, during all stages of a disease. However, in some cases, the immune system is overwhelmed by e.g. the rapid development of a disease or it fails in recognizing the pathogenic agent and needs support to resume its defense work. Immune enhancers are compounds able to stimulate the immune system and trigger the right immune response.

Role of the invariant natural killer T (or iNKT) cell agonists 

Invariant Natural killer T (iNKT) cells play a central role in connecting innate immunity and adaptive immunity.

iNKT cell is a distinct population of T lymphocytes that can rapidly release massive amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor (TCR) with glycolipids presented by CD1d. They can modulate immune responses by orchestrating other immune cells, including T cells, B cells, natural killer (NK) cells and dendritic cells (DCs). This orchestration can be done by direct interaction of iNKT cells with others cells or by secretion of cytokines, which can promote cell-mediated immunity to kill tumor cells and intracellular pathogens, or suppress autoreactive immune cells in autoimmune diseases. Thus, NKT cell is an attractive target for developing new therapeutics to enhance the immune system.

Mechanism of action of the iNKT cell in killing tumor cells 

During its development, cancer creates a micro environment deleterious for the immune system. Cancer develops strategies to hide itself and/or blocks the function of the immune system. Immunotherapy uses the body's own immune system to help fight cancer. This can be done in two ways: Generate a new immune response against cancer cells or reinvigorate the existing non-efficacious immune response.

Due to the central role of iNKT cells, they are a valid target to initiate immunotherapy. 

 

immune enhancer graphic

 

Figure: Activation of iNKT cells to mediate anti-tumoral activities.

A) Direct activation by tumor cells expressing CD1d.

B) Indirect activation by cross priming with DC.

 

As pictured in the figure, activation of iNKT cells during immune-surveillance can occur either directly, through presentation of glycolipids by CD1d positive tumors, or indirectly, by cross-presentation of tumor lipids by APCs. 

1-Direct Killing

Some tumor cells express self-lipid in the context of CD1d. In this specific case, iNKT cells can be activated directly interacting with the CD1d positive tumor cells. Following this interaction, iNKT cell activation occurs, leading to the secretion of perforin and granzyme B, which lyse the tumor cells.

2-Indirect Killing

iNKT cells interact with DC which express tumor lipids through CD1d. Upon activation, NKT cells induce a cascade of immune reactions leading to the secretion of large quantity of cytokines like IFNg, IL4 & IL12. Moreover the interaction with DC leads also to the maturation, activation and licensing of the DCs, giving them the required help to sustain the immune response.

ABIVAX’s Immune enhancer platform is based on intellectual property licensed from the Scripps Research Institute (La Jolla, United States).