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 Applications

1. Precision Targeted Immuno-suppression

By targeting critical pathways specifically in Immature Dendritic Cells or Macrophages NapaJen's team has reached unprecedented immuno-tolerance and anergy states in 2 separate programs.

Antigen Specific Tolerance

HLA-incompatible allo-transplantation was achieved in pre-clinical solid organ models using an earlier generation anti-CD40 oligo-SPG complex. Short-term administration of this oligo-SPG complex peri-transplantation, in a heterotypic heart transplant model, resulted in permanent graft acceptance in a pre-clinical model. NapaJen is further advancing these findings towards the treatment of graft versus host disease for hematological cancer patients receiving stem cell transplantations with a new generation anti-CD40 oligo-SPG complex.

Anergy to Auto-antigen

By knocking down a target mRNA molecule specifically in monocyte derived macrophage cells, anergy (absence of normal immune response to a particular antigen) was achieved in inflammatory tissue models through two separate mechanisms: (1) downregulation of inflammatory interactions with tissue cells, and (2) suppression of migration of these macrophages to the inflamed site. NapaJen's team is advancing these findings applicable to the treatment of autoimmune-diseases.

2. Activation of Innate Immunity in Tumors

Cancer progression has been demonstrated to be promoted by inflammatory phenomena in the tumor microenvironment encompassing leukocytes infiltrating tumors, among which myeloid-derived suppressor cells (MDSCs) represent the most important players controlling immunosuppression. MDSC not only inhibit T-cell mediated anti-tumor immune response but also directly stimulate tumorigenesis, tumor growth and metastasis by enhancing neo-angiogenesis prompting further metastases. NapaJen's Team is developing several programs in this area.

Dectin-1-mediated MDSC Control

Taking advantage of the presence of Dectin-1 receptor on immature dendritic cells or macrophages in MDSC has given NapaJen the ability to selectively target these critical cellular players for cancer therapy through four approaches: (1) regain innate immunity responsive to tumor antigens by knocking down a key mRNA; (2) stimulate innate immunity through Toll receptors such as TLR9 and/or TLR3; (3) cell specific presentation of tumor antigen peptides in complexation with SPG; and (4) Oligo-SPG complexes targeting the tumor cells. These four approaches independently demonstrate efficacy and are expected to synergize.