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

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

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