Our Science

AbolerIS Pharma aims to develop molecules that regulate immune responses with high selectivity and potency.

The major objective is to induce immune tolerance in clinical situations in which tissues are attacked by destructive immune responses, as it happens in autoimmunity, solid organ rejection and graft-versus-host disease during bone marrow transplantation.

Since immune responses are also essential to fight infectious agents and cancer cells, preserving these responses is essential. Furthermore, certain molecules can have tolerogenic actions, and inhibition thereof may be advantageous in the context of fighting infection or cancer. Careful evaluation of these aspects has been taken into consideration with the molecules under development by AbolerIS Pharma.

In conclusion, AbolerIS Pharma’s pipeline has an integrated and complete view of immune responses and their different manipulations.

Project 1. Anti-CD45RC Mab

Description. This monoclonal antibody induces apoptosis of T cells expressing high levels of CD45RC, such as precursors of effector Th1 type cells and terminally effector T cells. These type of T cells destroy the tissues and inhibit also the development of T cells with suppression capacity, such as regulatory T cells, that can inhibit not only the effect of these pathogenic T cells but also other cells, such as antigen presenting cells involved in the development of immune responses. The final outcome of anti-CD45RC mAb therapy is to favor immune tolerance to restricted antigens and preserve immune responses to exogenous antigens.

AbolerIS Pharma develops several variants through the most updated recombinant antibody technologies, such as humanization, avoidance of amino acids bringing potentially unwanted post-translational modifications, different isotypes, etc

Potential clinical applications. Proof of concept of the tolerogenic effect of anti-CD45RC has been done in animal models of autoimmunity, solid organ rejection and graft-versus-host disease during bone marrow transplantation. A first clinical proof on concept will be done in one of these pathologies in the next 2 years and others at later stages of development.

Project 2. IL-34.

Description. IL-34 is a cytokine that acts primarily on the mononuclear phagocytic system sustaining macrophage generation and differentiation. It acts through the CSF-1R, thus sharing actions with CSF-1, but also through PTPzeta and CD138 receptors or co-receptor expressed by other cells. Activation of monocytes and macrophages in the presence of IL-34 drives differentiation of tolerogenic M2-type macrophages. M2 macrophages favor the development of Treg. IL-34 treatment induces and strengthens tolerogenic mechanisms.

AbolerIS Pharma is developing new muteins with increased affinity compared to wild-type IL-34 that are either agonists or antagonists and fusion molecules with increased half-life and tissue targeted action.

Potential clinical applications. A first area of application of IL-34 muteins is the use of agonists in neuroinflammatory conditions by decreasing inflammation through actions on microglia as well as by having trophic actions on neurons and astrocytes. A second area of application of IL-34 muteins is the use of antagonists that bind to its receptors but do not transduce cell signals and compete with wild type IL-34. Cancer and bone diseases with excessive bone reabsorption are among these diseases.