Details

Project TitleModulation of Immune Function by the Targeted Enhancement of CD154 Trimer Stability
Track Code2005-008
Short Description

Northwestern researchers have identified a lead compound that can enhance immune function in vivo through a novel mechanism of stabilizing the CD154 trimer on the surface of activated T cells.

#therapeutics #cancer #infectiousdisease #autoimmunity

Abstract

The CD154 antigen (CD40L) is central to type 1 helper T cell immune response and immune effector function. Though it is important, the active CD154 trimer is extremely transient. The aim of this study is to develop a new therapy for either inhibiting immune cell function in autoimmune disease, or enhancing natural or vaccine facilitated immune responses through the stabilization of the CD154 trimer. The identification of a small molecule that can enhance immune response by this mechanism is the first successful scientific study to do so.

The process of discovering candidates began with docking studies using a molecular model of the CD154 trimer, identifying potential small molecule binding sites and screening over 250,000 compounds. Positive candidates were screened visually, and a small number were selected for in vitro testing, of which two appeared to stabilize the trimer. Initial in vivo studies in a mouse model showed the ability of the compound to enhance an immune response. Additionally, preliminary results from a mouse cancer model show promising results in both tumor reduction, and decreased metastasis.

 
Tagsautoimmunity, THERAPEUTICS: infectious disease, THERAPEUTICS: cancer
 
Posted DateMay 2, 2011 7:01 PM

Inventor(s)

Laurence Howard

Brian Shoichet

John Irwin

Stephen Miller*

Applications

• Vaccine therapy: protect against infectious or toxic agents

• Therapeutics: autoimmune disease, cancer, infectious disease, immunotherapy

Advantages

The compound is the first demonstrated to enhance immune function in this way. The molecules can be applied to:

  • Chemotherapeutic strategies -targeting and eliminating cancer cells
  • Standalone vaccines -protect against infectious or toxic agents
  • Treating infectious disease -antibiotic facilitator enhancing immune function
  • Facilitator for immune clearance of persistent infections
  • Boosting immune response in compromised individuals

IP Status

Issued US Patent No. 7,601,355

Contact Information

Michael Moore, PhD
Invention Manager
(p) (847) 491-4645

(e) michaelmoore@northwestern.edu