Table 2 Comparison of traditional ACT and enhanced cellular therapy

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