CAR-CIK Solid Tumors
Adaptation of CAR-CIK technology for solid tumors
- Solid tumors constitute 95% of the cancer market
- Demonstrated ability of CAR-CIK effectiveness against solid tumors
- Several patients in the ALL trial developed solid tumors (liver, CNS, Uterus) which resolved after CMN-005 infusion
- CAR-CIK cells may be more effective against solid tumors than CAR-T cells but are likely to require additional technologies in these settings
- CAR-T cells have proven to be ineffective against solid tumors due to the tumor microenvironment and significant safety issues due to off-tumor effects

Research collaborations at MSK
New technologies:
- SEAKER CAR1 (Synthetic Enzyme-Armed Killer Cells): Expresses prodrug converting enzyme (e.g., Carboxypeptidase G2 or B-lactamase) to achieve high active anti-tumor drug levels at tumor sites
- SHIELD CAR2: Expresses the IgG protease ides2 to prevent antibody-based elimination of cells
- Orexi-CAR3: Expresses a secreted form of a high affinity variant of SIRPa to downregulate the ‘do not eat me’ signal (CD47) on tumor cells to relieve tumor microenvironment immunosuppression
- IL-18 CAR4: Expresses a secreted form of IL-18 to improve proliferation, persistence and reverse immunosuppression in the tumor microenvironment
- Solid tumor CAR target identification and validation
1Cancers (2021) 12:2175; Accepted Nature Chemical Biology
2Mol Ther. (2021) 29:10
3Unpublished
4Cell Reports (2018) 23:2130-2141
Non-viral gene transfer technology accelerates development

Each technology requires the addition of another gene in addition to the CAR receptor
We simply produce pT4 vectors encoding each new gene
Plasmids can be mixed and matched and co-electroporated to customize functionality to each solid tumor indication