CAR-NK therapy builds upon allogeneic NK Cells (“Natural Killer”)
providing the NK cells with the information necessary to recognize, target, and destroy cancer cells. CAR-NK technology is proving to be a superior alternative to CAR-T, with many advantages such as multifunctionality, low toxicity, and universal patient applications, i.e., not patient-specific.
CAR-NK Sources and Application
CAR-NK: Challenges and Cellicure’s Solutions
In order to achieve full NK cell activation the inhibitory receptor signaling barrier must be overcome.
Complete signaling CAR-NK platform, (csCAR-NK)
The novel optimized csCAR provides the NK cell with a complete signaling cascade that results in a fully activated NK cell. Cellicure’s csCAR-NK efficiently overcomes the NK cell inhibitory receptor barrier.
Because NK cells have a short lifespan, cytokines are often introduced to support cell survival and growth.
Cytokine-free, renewable, long-term NK platform (reNKTM)
Using Cellicure’s innovatively designed, gene-engineered SafteinTM, the reNK cells renew and achieve long-term survival. As a result, in vitro or in vivo cytokine injection is no longer necessary.
Current NK cell expansion technology can be inefficient and not cost-effective.
Non-feeder cell supported NK expansion platform, (Effic-NKTM)
The novel Cellicure Effic-NKTM expansion system has a simplified cell culture setup and does not require feeder cells for continued cell proliferation. Effic-NKTM also has an increased expansion efficiency, allowing the final NK cell product to have exceptional and highly integrable functional abilities.
Cellicure csCAR vs. Classical CAR
The classical CAR backbone is composed of 4 components:
- Single-Chain Variable Fragment (scFv)
- Transmembrane/costimulatory signal (signal 2)
- CD3zeta activation signal (signal 1)
(See Classical CAR graphic above)
Current solutions do not effectively overcome the NK cell inhibitory receptor signal barriers.
Based on NK biology and NK receptor signaling properties, Cellicure has developed the “Complete Signaling CAR (csCAR)” solution.
This innovative technology overcomes the challenges of the receptor cell barrier by deploying the patented and innovative signal 3 and 4 elements as well as our own hinge and transmembrane domain.
Cellicure Renewable NK (reNKTM) vs. Classical NK Cell Therapy
Traditionally, NK cell survival and growth require cytokine signaling such as IL-2 and IL-15. Membrane-bound (mb-) cytokines such as mb-IL-15 and other receptors also provide sufficient signaling to support NK cell survival and growth. However, the side-effects of these cytokines include immunosuppression and toxicity that leads to reduced efficacy or failed therapy.
Cellicure has developed an innovative, gene-engineered “safe protein” called “SafteinTM,” for renewable NK (reNKTM) cells.
Expression of Cellicure’s membrane-bound SafteinTM on the surface of NK cells supports NK cell survival and renewal that is equal to or better than current cytokine-based treatments. SafteinTM does not cause the toxicity and immunosuppression issues commonly seen with cytokine use.
NK Expansion System (Effic-NKTM)
Cellicure has developed an innovative NK cell expansion system (Effic-NKTM), which is feeder-free, and has a simplistic culture setup.
Cellicure’s Effic-NKTM system has a high cell expanding efficiency. Most importantly, the final Cellicure NK product achieves a high cellular yield with intact functionality.