Table 2. Comparison of key delivery platforms for in vivo CAR-T engineering.

Platform	Targeting Strategy	Persistence	Safety Concerns	Translational Status	Refs
Lentivirus	Engineered envelope proteins (e.g., NiV glycoprotein with CD8-specific DARPin/scFv)	Integrating (Long-term)	Insertional mutagenesis, immunogenicity, off-target transduction	Early clinical (e.g., INT2104, ESO-T01)	[102–104]
AAV	Capsid engineering for tropism modification	Episomal (Long-term expression)	Pre-existing immunity, off-target effects, immunogenicity	Early clinical & Preclinical	[101,105,106]
LNP	Antibody-conjugated or immunotropic lipid formulations	Transient (mRNA-based)	Reactogenicity, infusion reactions, hepatotoxicity	Early clinical (e.g., CPTX2309)	[107,108]
Exosomes	Surface-displayed targeting ligands (e.g., anti-CD3/CD28 scFv)	Transient (mRNA-based)	Manufacturing scalability, payload loading efficiency, biodistribution control	Preclinical	[109,110]
Scaffolds	Localized, sustained release of CAR construct + T-cell ligands	Sustained (depends on cargo)	Biocompatibility, local inflammation, surgical implantation	Preclinical	[111–113]

Note: Abbreviations: AAV: Adeno-associated virus; DARPin: Designed ankyrin repeat protein; LNP: Lipid nanoparticle; NiV: Nipah virus; scFv: single-chain variable fragment