In situ antigen modification-based target-redirected universal chimeric antigen receptor T (TRUE CAR-T) cell therapy...

Area of Science:

• Immunotherapy
• Oncology
• Nanotechnology

Background:

• Chimeric antigen receptor (CAR)-T cell therapy is highly effective against blood cancers but faces challenges in treating solid tumors.
• The limited success in solid tumors is often due to the scarcity and variability of target antigens on cancer cells.

Purpose of the Study:

• To develop a universal CAR-T cell therapy approach for solid tumors.
• To overcome the limitations of target antigen availability in solid tumors.

Main Methods:

• Developed a target-redirected universal CAR-T (TRUE CAR-T) cell therapy modality.
• Utilized fusogenic nanoparticles (F-AgNPs) to deliver exogenous antigens for in situ modification of solid tumor cell membranes.
• Evaluated modification effects using flow cytometry and confocal microscopy.
• Assessed in vivo behavior of F-AgNPs using near-infrared imaging.
• Tested the combined therapy in subcutaneous and disseminated tumor models.

Main Results:

• F-AgNPs successfully modified tumor cell membranes via fusion, with antigens spreading into tumor tissues.
• This in situ modification activated CAR-T cells and induced antitumor immune responses against various tumor cell types, irrespective of their native antigens.
• The combination of F-AgNPs and CAR-T therapy significantly inhibited tumor growth and extended survival in preclinical models.

Conclusions:

• Fusogenic nanoparticle-mediated in situ antigen modification overcomes antigen deficiency and heterogeneity in solid tumors.
• This approach enhances CAR-T cell efficacy and expands their applicability for solid tumor immunotherapy.
• Established a novel TRUE CAR-T cell modality with broad potential for solid tumor treatment.