Chimeric Antigen Receptor (CAR) modified Cytokine Induced Killer (CIK) cells
Coimmune’s CAR-CIK immunotherapy platform distinguishes itself in three key ways from other CAR-T approaches.
Differentiated Immune Cells
CoImmune’s novel approach leverages the properties of Chimeric Antigen Receptor (CAR) technology to activate the immune system in a rapid, potent, and direct manner against cancer. Coimmune’s technology is distinctive in that it uses a different kind of immune effector cell for CAR directed therapy. Namely Cytokine Induced Killer (CIK) cells rather than T cells. CIK cells are lymphocytes that also have Natural Killer (NK) cell-like properties, even though 95% of the CIK cell population has the CD3+, T cell phenotype. The NK-like properties involve immune- cell activation mechanisms different from T cells, in that the NK-like anti-tumor response is non-MHC restricted. Because of these additional features, CIK cells may have a broader therapeutic impact. Leveraging both anti-tumor properties of both NK cells and conventional T cells.
CAR–CIK cells are engineered with receptors that target surface antigens of interest expressed on tumor cells. CAR–CIK cells engage the target antigen via a single-chain variable fragment (scFv) derived from a monoclonal antibody. The scFv is coupled to a hinge region, a transmembrane and an intracellular signaling domain. This CAR makes important contributions to the interaction with antigen, assembly of the immunologic synapse, and association of the CAR–CIK cells with other proteins necessary to transduce a robust activation signal. These engineered CAR-CIK cells are designed to promptly activate upon their detection of the relevant tumor antigens, triggering cytotoxic activity, and release of cytokines within the tumor microenvironment.
These reprogrammed targeted CAR-CIK cells are then infused into the cancer patient to subsequently eliminate the targeted tumor cells. Recent data accumulated over the past 18-24 months from clinical trials have demonstrated the capacity of CAR-CIK cells to effectively eradicate treatment-resistant cancers within a matter of weeks, even when patients present with a large tumor burden.
Off the shelf...
CIK cells have been shown to be well tolerated with no incidence of Graft versus host disease (GvHD), a potential life-threatening result from traditional CAR-T therapies. By producing CAR-CIK cells from cord blood offers even further protection against GvHD. The majority of immune cells in cord blood are ‘inexperienced’ which means they are less responsive to allo-stimulation and have low effector cytokine production which decreases the incidence of GvHD, a common problem associated with all forms of allo– T cell therapies prepared from adult peripheral blood.
Furthermore, producing CAR-CIK cells from cord blood offers the opportunity for an off-the-shelf therapy owing to the lower degree of tissue match required for the recipient, meaning that a relatively small product bank could achieve broad population coverage. Additionally, repeat dosing of patients without significant safety risks may be possible to improve long-term outcomes. CoImmune believes that the switch to cord blood from adult PBMCs can increase safety, making the off-the-shelf model feasible and allow repeat dosing while preserving the already impressive efficacy signal emerging from on-going clinical trials.
NON-VIRAL genetic modification of CAR-CIK cell population
Historically, CAR-T cells have been genetically engineered using lenti-viral or retro-viral transfection methods. These methods have been used successfully in specialized laboratory settings for small- scale production. Distinct from most commercially developed CAR-T therapies, Coimmune adopts a proprietary non-viral transfection method for the creation of CAR-CIK-based therapies.
Coimmune leverages a non-viral method of stable gene transfer as an alternative to viral vectors, with the intent to overcome practical, regulatory, and manufacturing scale-up limitations related to viral transfection methods. Also, the expression cassette of the non-viral transfection method is integrated by a non-homologous recombinant mechanism, resulting in a safer, random gene insertion, compared to retro-viral vectors that display a marked tendency to target gene promoters. The latter of which leads to an increased probability to deregulate the expression of the targeted genes.
The proprietary manufacturing of Coimmune’s CAR-CIK may offer a more streamlined and less complicated route to commercialization.