From: Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy
Enhancement strategy | Target | Aim | References |
---|---|---|---|
Cytokine co-expression | IL-12 | Improve persistence | Koneru [203] |
Improve anti-tumor activity | Pegram [204] | ||
IL-15 | Liu [30] | ||
Krenciute [205] | |||
IL-18 | Avanzi [206] | ||
Hu [207] | |||
Cytokine/JAK/STAT co-expression | IL-2Rβ + STAT3/5 | Improve persistence | Kagoya [208] |
Improve anti-tumor activity | |||
Cytokine receptor co-expression | IL-7Rα | Improve persistence | Shum [209] |
Improve anti-tumor activity | |||
Chemokine co-expression | CCR2, CCR2b, CCR4, CCR7, CXCR2, CXCR4 | Promote trafficking into tumor microenvironment | Brown [210] |
Craddock [211] | |||
Moon [212] | |||
Rapp [213] | |||
Di Stasi [214] | |||
Carlsten [215] | |||
Kershaw [216] | |||
Hillerdal [217] | |||
Dual CAR (two antigens required for activation) | BCMA + CS1 | Enhanced safety and efficacy | Chen [218] |
Split CAR (separation of co-stimulatory domains) | PSMA + PSCA | Achieve tumor-specificity in the absence of a truly tumor-restricted antigen | Kloss [219] |
Multi-antigen targeting (bi-specific CAR) | HER2 + IL13Rα2 | Improve anti-tumor activity | Hegde [220] |
HER2 + IL13Rα2 + EphA2 | Prevent antigen escape | Bielamowicz [221] | |
Universal CAR | CD16 (Fc receptor) | Precise control of CAR reactivity based on Ab half-life | Caratelli [222] |
Antibody tag | Re-use of approved antibodies, requiring only one CAR construct | Tamada [223] | |
Feldmann [224] | |||
FITC | Tamada [223] | ||
Inhibitory CAR Controllable CAR expression systems | Healthy tissue antigen, e.g., CD19 (with inhibitory domain, e.g., PD-1, CTLA-4) | Improve specificity, better discrimination healthy and tumor tissue | Fedorov [225] |
Syn/Notch | Controlled CAR expression | Morsut [226] | |
Inducible co-stimulation | Inducible CAR activation | Mata [227] | |
Knockout of checkpoint inhibitor | PD-1 | Improve persistence | Rupp [228] |
Improve anti-tumor activity | Ren [229] | ||
Cherkassy [194] | |||
Daher [70] |