Monoclonal antibodies (mAbs) that stimulate anti-tumor immunity are important drugs for cancer therapeutics. Agonistic antibodies targeting immunostimulatory receptors on T cells and antigen-presenting cells can also stimulate anti-tumor immunity, which is a promising field of cancer immunotherapy. Creative Biolabs is a service provider with more than 10 years' experience in antibody development. We believe that we will provide comprehensive and high-quality services for your checkpoint agonistic antibody development.

Introduction of Checkpoint Agonistic Antibody

Over the past decade, cancer immunotherapy has positively changed the results and basic concepts of cancer treatment. Most of these breakthroughs are due to the discovery and treatment of key immunoregulatory molecules (checkpoints) at the interface between the immune effector and the tumor microenvironment. The basic biological concept used in these treatments is to release a potentially effective adaptive immune response to tumors. In addition to the known negative regulatory axes of cytotoxic T lymphocyte associated antigen-4 (CTLA-4/B7) and programmed death-ligand 1 (PD-L1) with its receptor, programmed cell death protein 1 (PD-1), effective adaptability and innate immune response induction are also regulated by a set of activation signals. They are mainly mediated by costimulatory molecules, which are usually expressed briefly after activation of the first T cell receptor (TCR). They are usually members of the immunoglobulin superfamily or tumor necrosis factor (TNF) receptor (TNFR). The discovery of co-stimulator promotes preclinical and clinical trials of excitatory antibodies, which have potential applications in a variety of tumor environments, especially when combined with simultaneous blocking of inhibitory checkpoints.

Checkpoint Agonistic Antibody Development Service in Creative Biolabs

The use of agonistic mAbs has become one of the most effective ways to improve the immune response to infectious sources or to activate the immune response to cancer cells. Based on our unique phage display platform and antibody engineering platform, we provide many exciting customized development services for checkpoint proteins. These checkpoints are described in detail as follows:

• Custom Anti-TNFR-SF (TNFR-Superfamily) Agonistic Antibody Development Service

TNFR-SF receptors are central regulators of immunity, cell proliferation and death, and other important biological processes. Many co-signaling TNFRSF members are expressed in activated T lymphocytes, and their specific ligands are expressed in specialized antigen presenting cells (APCs), neutrophils, macrophages or stromal cells. The ligands and agonist antibodies can activate these receptors to stimulate T cell proliferation and activation. For example, activation of CD40 expressed on antigen-presenting cells has been shown to promote the more efficient presentation of tumor antigens to activated T cells. At present, there is a great deal of evidence that anti-TNFR-SF agonist antibody is promising cancer immunotherapy.

Fig.1 The TNFR-SF of co-stimulatory receptors. (Mayes, 2018)

• Custom Immunoglobulin B7-CD28 Family Development Service

The immunoglobulin B7 family is composed of structurally related cell surface protein ligands that bind to the CD28 receptor family on lymphocytes and regulate immune responses through co-stimulation or co-suppression signals. Anti-agonist antibodies to co-stimulatory receptor B7-CD28 targeting immune checkpoints are very important in driving productive anti-cancer immunity and have strong genetic evidence to support their role in mediating anti-cancer immune response.

Fig.2 Costimulation and coinhibition of B7-CD28. (Collins, 2005)

• Custom Anti-IL-2 Agnostic Antibody Development Service

Interleukin-2 (IL-2) is a cytokine signaling molecule in the immune system. It plays a central role in activating CD4+ and CD8+ T cells and regulatory T cells (Tregs) through high-affinity IL-2 receptors composed of αβ and γ subunits. We have demonstrated that the so-called agonist to anti-IL-2 mAb can selectively stimulate CD4+ Treg cells or CD8+ T and NK cells, so they can regulate specific immunity without immunosuppression, and in many cases provide a promising way for Treg therapy.

• Custom Anti-STING (Stimulator of Interferon Genes) Agnostic Antibody Development Service

STING is an endoplasmic reticulum (ER) resident molecule, which is the confluence of pattern recognition receptor (PRR) and cytosolic DNA receptor found in recent years, and participates in host-pathogen interaction. It directly senses circulating dinucleotides (CDNs), which are important messengers of innate immune agonists in bacteria and mammals.

Features of Our Services

• The efficient technology platform and experienced team
• Customized antibody development service to specify the best solution for your experimental system and objectives
• High purity antibody with very low endotoxin levels, and no preservatives or stabilizers
• Good after-sales and short turnaround time

If you are interested in our custom checkpoint agonistic antibody development service, please feel free to contact us.

References

1. Mayes, P.A.; et al. The promise and challenges of immune agonist antibody development in cancer. Nature reviews Drug discovery. 2018, 17(7): 509.
2. Collins, M.; et al. The B7 family of immune-regulatory ligands. Genome biology. 2005, 6(6): 223.

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