NKT cells are master regulators of immunity. NKT cell activation triggers recruitment of antigen presenting dendritic cells, antibody producing B cells, Natural Killer (NK) cells, and T cells while inhibiting myeloid derived suppressor cells, a cascade of events that cooperate in generating effective immune responses. An important limitation to developing NKT cell activators that promote immunity against infection and cancer is that potent ligands can induce subsequent NKT cell unresponsiveness that prevents continued stimulation and function of these important cells. Vaccinex and its academic collaborators have invented novel NKT cell agonists that minimize or prevent such unresponsiveness. Moreover, by combining these ligands in bispecific molecules with a targeting moiety, this strategy is being applied to target NKT cells to the site of antigen presentation so as to enhance vaccine induced immune responses and, in the special case of cancer, to target NKT cells to tumors so as to enhance tumor-specific immunity through recruitment and activation of cytotoxic T cells and antibody armed NK cells able to eradicate the tumor.
• Target natural killer T cells (NKT) to the tumor site
• Avoids induction of energy by substituting soluble CD1d for presenting cells
• Couples all of the elements required for NKT stimulation into a single stable covalent complex
– Glycolipid, CD1d, and tumor targeting agent
Supporting, Vaccinex-affiliated publications:
CD1d-antibody fusion proteins target iNKT cells to the tumor and trigger long-term therapeutic responses.
Corgnac S, Perret R, Derré L, Zhang L, Stirnemann K, Zauderer M, Speiser DE, Mach JP, Romero P, Donda A. Cancer Immunol Immunother. 2013 Apr;62(4):747-60. doi: 10.1007/s00262-012-1381-7. Epub 2012 Dec 15.
Sustained activation and tumor targeting of NKT cells using a CD1d-anti-HER2-scFv fusion protein induce antitumor effects in mice.
Stirnemann K, Romero JF, Baldi L, Robert B, Cesson V, Besra GS, Zauderer M, Wurm F, Corradin G, Mach JP, Macdonald HR, Donda A. J Clin Invest. 2008 Mar;118(3):994-1005. doi: 10.1172/JCI33249.