Anti-IL-2 Agonistic Antibody Introduction

Agonist antibodies targeting immune co-stimulatory receptors in cancer show great potential in the treatment of diseases, especially cancer. Therefore, the development of agonist antibodies targeting immune co-stimulatory receptors in cancer is an emerging direction for drug development. The desired characteristic of agonist antibodies is the ability to bind and activate target receptors in a manner that mimics natural ligand activity. Whether an antibody can act as an agonist is influenced by many factors, including binding epitope, affinity, potency, degree of receptor occupancy, and the interaction of the structural domain of the crystallizable fragment (Fc) of the antibody with the Fc gamma receptor (FcγR). Based on our rich field experience and advanced research platform, Creative Biolabs provides comprehensive services to support custom agonistic antibodies and checkpoint agonistic antibodies.

Interleukin-2. (Creative Biolabs Authorized) Fig 1. Interleukin-2.

Anti-IL-2 Agonistic Antibody

IL-2 is a multifunctional cytokine secreted primarily by CD4-positive T cells. It regulates the immune response by binding to the IL-2 receptor (IL-2R). There are two types of IL-2R—high affinity IL-2R consists of three subunits, α-chain (CD25), β-chain (CD122), and γ-chain (CD132). High-affinity IL-2R is mainly expressed on the surface of Treg cells, newly activated CD4-positive and CD8-positive effector T cells, some natural killer (NK) cells, and NKT cells. The medium-affinity IL-2R consists of two subunits, CD122 and CD132, which are mainly expressed on the surface of CD8-positive memory T cells and most NK cells. IL-2R signaling not only affects the proliferation of effector T cells, Treg cells, NK cells, and other cells but also shapes their functional activity.

Previously, IL2 antibody-based agonist antibody therapies focused on selectively activating CD8+ T cells but not Treg cells. However, several pharmaceutical giants and research institutes have changed their strategies and started to emphasize favoring Treg. The key point lies in CD25 (IL-2Rα chain), which is the IL-2 receptor component chain on Treg cells (IL-2Rαβγ on Treg cells, IL-2Rβγ on CD8+ T cells), and it is easier to bind IL-2 to make Treg more sensitive to low-dose IL-2. In addition, FAP-IL2v is also a potential direction. A new cytokine, PD1-IL2v, was designed after FAP-IL2v, in combination with a PD-1 blocker, was able to induce the differentiation of stem-like CD8+ T into a Teff subpopulation with more potent effects. It is able to first recognize and block the PD-1 receptor, then bind IL-2R to activate IL-2 signaling, and finally obtain a stronger effector function than PD-1 blockers in combination with FAP-IL2v.

Antagonists are generally designed with antibodies that have the highest affinity and are able to compete with the ligand for binding to the receptor's ligand-binding domain. Unlike the design of antagonists, there are no hard-and-fast rules for the design of agonists. A detailed understanding of the binding properties of natural ligand-receptor complexes can help in designing the optimal agonist antibody for a particular receptor. Receptor structures, ligand-binding mechanisms, and signaling mechanisms usually tend to be conserved within receptor families but are highly distinctive across families. Therefore, we should independently consider the mechanisms of co-stimulatory receptor binding and activation for different classes of cancer immune agonists.

Creative Biolabs has a wealth of knowledge and experience in antibody discovery. We would be happy to share with you our knowledge and experience in agonistic antibody discovery and anti-IL-2 agonistic antibody discovery.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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