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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