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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
CAR-T solid tumors abstract

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
1Nat Chem Biol. (2022) 18(2):216-225 2Mol Ther. (2021) 29:10 3Blood (2023) Online ahead of print 4Cell Reports (2018) 23:2130-2141

Non-viral gene transfer technology accelerates development

non viral transfer image
  • 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