CMN-008 (Armored CAR-CIK cells)
Armored Chimeric Antigen Receptor (CAR) modified Cytokine Induced Killer (CIK) cells
CMN-008 (Armored CAR-CIK cells)
Technology acquired from Memorial Sloan Kettering
- CIK cells genetically modified using SB100X mRNA + pT4 vector encoding both CD19 CAR and IL-18
- Referred to as ‘armored CAR’
Constructed a bicistronic vector encoding both CAR-CD19 and IL-18
- The transposon inserted into the chromosome contains both genes (shown in red)
- Ensures that all CAR+ cells are IL-18+
CMN-008 addresses the market concerns
Safety
- IL-18 only secreted in the presence of CD19+ cells (no systemic toxicity observed)
- Does not require lymphodepletion in animal models (game changer if same true for patients)
- Suitable for outpatient usage and administration at community sites (allo product avoids complex autologous logistics)
- Lower dose required for same efficacy in animal models
Efficacy
- Increased anti-tumor activity
- Increased in vivo expansion (unaffected by homeostatic cytokines)
- Enhanced persistence and durability of responses (deeper and longer lasting B cell aplasia in animal models)
- Recruits other types of immune cells for a more complete anti-tumor response (CD8+ , NK, NKT, dendritic cells)
Reduced lead time
- Requires only a 17-day process (current autologous therapies have 3-4 week lead time)
Affordability will ease reimbursement issues
- Streamlined manufacturing process and replacing retrovirus with Sleeping Beauty 100X greatly reduces COGS
Armored CAR technology works with CIK cells
Test article
Built-in safety – No IL-18 secretion without tumor cells present
IL-18 secreted only when stimulated with tumor cells
*REH cells: CD19+ tumor cell line
CMN-008 more than doubles the anti-tumor activity of CMN-005
Enhanced functionality vs REH cells with IL-18 expression
Published data (Cell Report (2018) 23:2130-2141)
IL-18 CAR-T cells fully effective even without lymphodepletion
- Standard CAR-T cells are not effective without lymphodepletion
- Armored CAR-T cells are highly effective even without lymphodepletion (Top)
- IL-18 is responsible for the enhanced activity since armored CAR-T cells are ineffective in IL-18 receptor knockout mice (Bottom)
IL-18 CAR-T have improved properties
- Armored CAR-T cells expand rapidly in vivo (Top right)
- Armored CAR-T cells induce deeper and durable B cell aplasia i.e., anti-leukemia effect (Bottom right)
- Armored CAR-T cells recruit other immune cells to the bone marrow (Below)
Cell Reports 23, 2130–2141, 2018
