The S-TIR™technology is an active checkpoint Control immunotherapy (ACCI) for the treatment of Cancer. The platform that was originally developed by S-TARget therapeutics GmbH for the treatment of severe allergic diseases and out-licensed for oncology to OncoQR ML.
Like all vaccines based on this platform, the ACCI is a complex of two modules – a “warhead” and an “immunogen”:
Module 1, the “warhead”, is designated to combine 4 major elements and functions:
- Binding to plasmacytoid dendritic cells (pDCs) through specific interaction with FcgammaRIIa (CD32a), which facilitates enhanced and specific uptake of the vaccine by the relevant professional antigen presenting cells (APCs). pDCs are a rare subset of circulating dendritic cells which can be found in blood, skin and in peripheral lymphoid organs and which express both CD32 and TLR9.
- Triggering of pDCs to produce large amounts of Th1-inducing cytokines through a specific interaction with the Toll Like Receptor 9 (TLR9), which therefore serves as intrinsic “adjuvant”. Activation of TLR9 primes pDCs to break tolerance against tumour associated antigens present in module 2.
- Binding to module 2 specific B cells through a low affinity interaction with CD32b on the B cells together with a (most likely) low affinity interaction with the B cell receptor specific for module 2.
- High-affinity binding to the “immunogen” through a specifically designed dimerization motive that connects with its counterpart in module 2.
Module 2, the “immunogen”, part of the drug, combines 2 basic elements:
- Activation of tumour specific T and B cells
- High affinity binding to the warhead through a specifically designed dimerization motive that connects with its counterpart in module 1.