Recent advances in T-cell engineering for use in immunotherapy.

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Adoptive T-cell therapies are effective against B-cell malignancies.
• Two main strategies exist: T-cell receptor (TCR) and chimeric antigen receptor (CAR) engineering.
• Recent advances are crucial for expanding efficacy, particularly against solid tumors.

Approach:

• TCR-based therapy involves engineering T cells to recognize cancer-specific peptide/MHC complexes.
• CAR-based therapy involves introducing synthetic receptors with antibody variable domains and signaling components.
• This review highlights recent significant advances in both TCR and CAR strategies.

Key Points:

• Optimal CAR configurations are under investigation for improved efficacy against solid tumors.
• The dimensions and stoichiometries of CAR/antigen complexes at the immune synapse are gaining attention.
• Neoantigens, identified as targets for endogenous T cells, present new opportunities for TCR-based adoptive therapies.

Conclusions:

• Recent innovations in CAR and TCR engineering are vital for advancing cancer immunotherapy.
• Understanding CAR/antigen interactions and leveraging neoantigens are key future directions.
• These strategies hold significant potential for treating a wider range of cancers, including solid tumors.