Emerging Immune Checkpoints - DDRs

Immunotherapy offers new avenues for tumor treatment with unique advantages and great potential, and immune checkpoint blockade is an important component of immunotherapy. PD-1 and CTLA4 are currently the most commonly used targets for immune checkpoint inhibition.

Now, we also need to discover more immunotherapeutic targets to provide more options for immunotherapy. Creative Biolabs is an expert in the field of immune checkpoint research and we are committed to continuously discovering new therapeutic targets and developing new immune checkpoint inhibitors. Here, we introduce an emerging immune checkpoint: DDRs.

Introduction to DDRs

DDRs, known as Discoidin Domain Receptors, are composed of DDR1 and DDR2 and are important members of the superfamily of collagen-activated Receptor Tyrosine Kinases (RTKs), a class of multi-structural domain collagen receptors.

Fig. 1 Regulatory mechanisms of DDR1/DDR2 in biological development, immunomodulation, cancer cell proliferation, invasion/migration and epithelial to mesenchymal transition. (Gao Y, et al., 2021)

Studies have shown that DDRs are expressed in dendritic cells, macrophages, microglia, neutrophils, and T lymphocytes, and are involved in the adhesion, migration, and secretion of immune cells through NF-κB, p38 MAPK, JNK, ERK, and other signaling pathways, thereby regulating the development of various diseases such as inflammation, fibrosis, and tumors.

R&D Status of Targeted DDRs

Tumor immunotherapy is currently being studied mainly in the form of DDR1. DDR1 plays an important regulatory role in the remodeling of the extracellular matrix (ECM) and mediates the formation of an immunosuppressive environment for tumors. Targeting DDR1 not only inhibits tumor progression, but also protects the body from future tumors.

• Number of marketed drugs: 0 (DDR1), 1 (DDR2)
• Highest stage of development: clinical phase I (DDR1), marketed (DDR2)

Research on DDR2 molecules has been making great progress for many years. However, the development of DDR1 drug targets is still in its early stages.

Development Strategies for Targeted Inhibition of DDRs

DDRs are expressed in a variety of immune cells and influence disease development through regulation of immune cells. Therefore, we explore the development of inhibitors targeting DDR as a potential therapeutic strategy and provide related research services.

• Development of small molecule inhibitors. A variety of small molecule inhibitors targeting DDR have been identified and tested in preclinical studies. We are committed to tailoring the most appropriate protocol to screen and identify the desired small molecule candidates with the desired function to meet your goals.
• Development of monoclonal antibodies. Monoclonal antibodies can be developed to target DDR and interfere with its function. We have an excellent infrastructure and technology platform to meet all the requirements of our customers to generate antibodies against DDR1 and DDR2 and test them in preclinical models.

Problems We Can Solve

The development of DDR antibodies and inhibitors is a complex process that requires addressing several challenges. These include:

• Understanding potential drug resistance mechanisms
• Optimizing the specificity and selectivity of inhibitors
• Developing and measuring biomarkers
• Developing preclinical models

Creative Biolabs is committed to providing a wide range of immune checkpoint development services, utilizing a comprehensive platform to collaborate with our clients to develop antibodies and inhibitors of immune checkpoint DDRs and help resolve difficulties encountered during the research process. Please don't hesitate to contact us.

Reference

1. Gao Y, et al. Discoidin domain receptors orchestrate cancer progression: A focus on cancer therapies. Cancer Science, 2021, 112(3): 962-969.

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