Immunomodulation Strategy for Enhancing Memory T Lymphocyte Immune Responses

 

Introduction

 

Cytotoxic T cells (T cells) are a type of immune cell that provide immunological protection by destroying cells that are perceived as abnormal. T cell exhaustion or inhibition is often observed in patients with chronic viral infections or cancer, resulting in a decreased ability of the patient to overcome such diseases. One strategy to enhance T cell responsiveness is to target inhibitory signaling pathways, such as the recently FDA approved PD-1 inhibitor pembrolizumab. This strategy has been shown to effectively reverse T cell exhaustion/inhibition and provides a tactic to boost patient resistance. In addition, studies have also shown that targeting T cell inhibitory pathways concurrent with vaccination may also enhance the efficacy of prophylactic vaccines, demonstrating several broad applications for T cell immunomodulators.

 

Description of Technology

 

Similar to that of PD-1, activation of CRACC receptors dampens T cell mediated immune responses. CRACC-Fc is a novel immunomodulator capable of enhancing T cell mediated immune responses by preventing inhibitory effects of CRACC activation on T cells. This inhibitory protein may be administered as a therapeutic to enhance T cell immune responses, or may be co-administered/co-expressed with an antigen to boost T cell responses for prophylactic vaccines. Preliminary studies have demonstrated that T cell proliferation and the production of antigen-specific cytokines are enhanced in CRACC-Fc treated mice, indicating an overall increase in T cell responsiveness. Although current work has been focused on the effects of the inhibitory protein on T cell responses, the CRACC receptor is expressed in multiple innate and adaptive immune cells (DCs, macrophages, NK cells, B cells) and it is possible that CRACC inhibition modulates the function of these immune cells as well, collectively resulting in enhanced immune response.

 

Key Benefits

  • Broad applications: This immunomodulator may be used in the treatment of a variety of diseases, or as a vaccine adjuvant
  • Acceptable by the FDA: Several Fc fusion proteins are FDA approved therapeutics
  • PD-1 synergy: CRACC and PD-1 feed into the same pathway with both dampening T cell immune responses upon activation. When both receptors are inhibited, an additive effect on T cell responsiveness is observed suggesting that co-administration may be used for further enhancement of T cell responses
  • Translatable: Although current in vivo studies have been in mouse, Fc-CRACC protein was designed for use in human without further modification

 

Applications

  • Cancer immunotherapy
  • Treat T cell exhaustion
  • Vaccine adjuvant
  • Use in conjunction with other therapies to produce synergistic effects

 

Patent Status

 

Patent application published, publication number WO2016049022

  

Licensing Rights Available

 

Full licensing rights available

 

Inventors

 

Andrea Amalfitano, Yasser Aldhamen

 

Tech ID

 

TEC2014-0105

 

Alternative contact due to temporary leave:

 

Nina (Isi) Davis, Technology Marketing Manager, email: davisnin@msu.edu, phone (direct): (517)884-1829. 

 

Patent Information:

Category(s):

For Information, Contact:

Su-Jun Lim
Technology Manager
Michigan State University
limsuju1@msu.edu
Keywords: