CAR Based Immunotherapy of Solid Tumours-A Clinically Based Review of Target Antigens

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Chimeric antigen receptor (CAR)-engineered immune cells have revolutionized hematological cancer treatment.
• Solid tumors remain a significant challenge for CAR-based immunotherapy due to complex tumor microenvironments and target heterogeneity.

Purpose of the Study:

• To review the clinical impact and challenges of CAR immunotherapy in solid tumors.
• To identify key targets and therapeutic strategies employed in clinical trials for solid tumors.
• To explore future directions for enhancing CAR T-cell efficacy and safety in solid tumor treatment.

Main Methods:

• Systematic review of clinical data for CAR T-cell therapies targeting solid tumors.
• Analysis of clinical trial outcomes for approximately 30 CAR T-cell targets.
• Evaluation of strategies including regional delivery, repeated dosing, and novel CAR designs.

Main Results:

• Clinical data are available for 30 CAR T-cell targets in solid tumors, with varying degrees of success.
• Significant challenges include immunogenicity and on-target, off-tumor toxicity, leading to severe adverse events.
• Regional delivery and repeated dosing strategies have been explored to improve therapeutic impact and safety.

Conclusions:

• CAR immunotherapy for solid tumors requires further optimization to overcome existing hurdles.
• Emerging approaches like "armoring" CAR T-cells and multi-targeted CARs offer potential for improved tumor targeting and safety.
• Continued research into novel CAR designs and delivery methods is crucial for advancing solid tumor CAR immunotherapy.