From: Enhanced cellular therapy: revolutionizing adoptive cellular therapy
Therapy | Mechanism | Advantages | Disadvantages | Examples | Category |
---|---|---|---|---|---|
CAR-T cell | Through genetic engineering, T cells are activated and installed with tumor Chimeric Antigen receptor | 1. Not MHC-restricted; 2. Strong signaling transduction through CD3ζ signaling pathway | 1. Restricted to cell surface antigens; 2. Complicated preparation process in vitro for each patient | Carvykti, Kymriah | ACT |
TCR-T cell | Using transgenic technology to install T cell receptors on T cells | 1. Sensitive recognition; 2. Strong signaling transduction through integrated T cell signaling pathway | 1. MHC-restricted; 2. Potential TCRs mismatch | Tebentafusp | ACT |
TIL | Endogenous TIL was isolated from the resected tumor, amplified in vitro, and then injected back into the patient | 1. Stronger tumor specificity; 2. More personalized | 1. short duration of cell activity; 2. Long cultivation and amplification time | LN-145 | ACT |
PD-1 antibody-enhanced CAR-T cell therapy | ICIs such as anti-PD-1\ PD-L1 antibodies can block the brake of immune and enhance the anti-tumor activity of CAR-T cells | 1. It prevent the failure of CAR-T cells and maintain its effector function 2. It makes up for the poor efficacy of CAR-T in solid tumors | 1. Cannot block other immunosuppressive mechanisms, such as CTLA-4 2. drug resistance | αPD-1-mesoCAR-T cells | Enhanced cellular therapy |
Interleukin-enhanced CAR-NK cell therapy | Cytokine drives the expansion and persistence of NK cells or other ATCs | 1. Non-antigen specific manner without causing GVHD; 2. Highly cytotoxic effectors | 1. Abnormal NK-cell proliferation or leukemia transformation lead by ectopic IL-15 production; 2. CRS | Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR | Enhanced cellular therapy |
PROTAC-enhanced TIL | PROTACs degrade unwanted proteins in ACTs to enhance efficacy | 1. Degradation of some inhibitors in TIL; 2. Increased T cell proliferation and reduced T cell failure | 1. Relatively high toxicity; 2. Unknown consequences due to less research | DeTIL-0255 | Enhanced cellular therapy |
Oncolytic Virus-enhanced CAR-T | Strong immune response induced by oncolytic virus infection to enhance the efficacy of CAR-T cells | 1. Promoted recruitment of CAR-T cells in TME by oncolytic virus; 2. More functional molecules expressed by modified oncolytic viruses | 1. Selection of appropriate oncolytic virus; 2. Faster removal speed of oncolytic virus reduced by CAR-T | OV19t-enhanced CD19-CAR T | Enhanced cellular therapy |