Haploidentical NK cell therapy
HAPLOIDENTICAL NK CELL THERAPY
NK cells are the gatekeepers of the innate immune system. They are able to efficiently kill cells in case activating ligands are present and signals for inhibitory receptors are absent.
After “danger” cell recognition, granules from natural killer (NK) cells release perforins and granzymes that induce apoptosis (programmed cell death) in target cells. This usually occurs against virus infected cells or tumor cells with diminished expression of class I MHC. However, normal unaltered cells remain unaffected. In addition, NK cells can bind antibody bound to a target cell and subsequently kill the target cell through a mechanism called Antibody Dependent Cellular Cytotoxicity (ADCC). NK mediated cell killing is a powerful mechanism to remove cancer cells leaving healthy cells intact. Haploidentical NK cells (i.e. from a family member) have a partial mismatch in killer inhibitory receptors and are thus more easily activated when stress ligands are recognized (which are very highly expressed on tumor cells). CiMaas has a long-standing research line on the use of donor NK cells in cancer. Pre-clinical and clinical research has demonstrated that the most optimal response is generated through an allogeneic Killer-cell Immunoglobulin-like Receptor (KIR) mismatched adoptive transfer using selected donor NK cells. Purposely mismatching KIRs by proper selection of donors circumvents the inhibitory effect of self-recognizing KIRs after infusion. CiMaas collaborated with American company Cytosen to develop an optimized NK cell expansion technology capable of producing more than 3x 1010 NK cells. This is a sufficient number to treat a patient. Until now, generating such large numbers of NK cells has been a major bottleneck in the development of adoptive NK cell therapies.
Cytosen has been acquired by Dutch biotech KiadisPharma on June 6, 2019, leading to a collaboration between Kiadis and CiMaas on further development of the NK cell production platform.
Characteristics of CiMaas NK cells:
- Expanded and activated cells
- Required cell numbers obtained
- Balance between activating and inhibitory receptors
- Highly active killing capacity against all tumors tested
- Enhanced killing in presence of monoclonal antibodies
- Active under hypoxic conditions