Immune System Modulators

Activation or Inhibition of the Immune System

The human body has evolved a complex immune system to effectively respond to pathogens and disease while making sure to minimize damage to healthy tissues. The immune system has multiple levels of regulation to ensure the appropriate balance between immune activation and immune suppression. Over the past decade some of the fundamentals of this regulation have become clearer, and this information provides new opportunities for the rational intervention of the immune system response that in combination with other treatments may lead to significant clinical benefit. Celldex is developing technologies and clinical programs with several immune system modulators.

• Toll-Like Receptor Agonists (TLR): TLRs are molecules in the immune system that respond to pathogen derived molecules and serve to alert and activate the immune system. Drugs that activate TLRs (TLR agonists) can simulate an infection and generate a strong immune response, particularly when combined with vaccines. Celldex has recently announced a clinical research collaborations with the 3M to access their proprietary Immune Response Modifier Resiquimod™ (and additional Toll-like receptor 7/8 agonists (TLR)) for clinical study with the Antigen Presenting Cell (APC) Targeting Technology.
• Complement Inhibitors: The complement system is a series of proteins that are important initiators of the body’s acute inflammatory response against disease, infection and injury. Excessive complement activation also plays a role in some persistent inflammatory conditions. Celldex has been developing a complement inhibitor called CDX-1135, a soluble form of naturally occurring Complement Receptor 1. CDX-1135 effectively inhibits the complement cascade in animal models, and has demonstrated safety and complement inhibition in human clinical trials. CDX-1135 is currently being assessed for therapeutic intervention in Antibody-Mediated Rejection (AMR) and other inflammatory conditions where the complement system is thought to have a critical role in the disease pathogenesis.
• Notch Binding Proteins: Using both allergy and transplantation model systems, it has been demonstrated that activation of the Notch signaling pathway in immune cells results in an antigen-specific immune suppression selective for the co-administered antigen. This finding may have significant commercial potential for the development of novel classes of therapeutics, and is the basis for our preclinical development program directed at type I (insulin-dependent) autoimmune diabetes and its complications. We have developed research programs with Notch binding proteins that trigger antigen-specific suppression of the immune system, resulting in inhibition of the pathological immune response without affecting other immune responses.

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