Modular (universal) CAR-T platforms in vivo: a comprehensive systematic review

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Modular CAR T-platforms address limitations of traditional CAR-T therapy by enabling multi-antigen targeting and controlled activity.
• These platforms utilize a universal receptor (signaling module) that interacts with a soluble module for antigen recognition.
• Several modular CAR-T platforms have been developed and some are progressing to clinical trials.

Purpose of the Study:

• To systematically review and evaluate the performance of various modular CAR T-platforms in preclinical animal models.
• To assess key performance parameters of modular CAR T-platforms in xenograft mouse models.

Main Methods:

• A systematic literature search was conducted in PubMed, Google Scholar, and BASE.
• Studies utilizing xenograft mouse models with any modular CAR T-platform variant were included.
• Quantitative findings, including standardized mean difference (SMD) and median survival rate (MSR), were extracted and presented using forest plots.

Main Results:

• 33 studies involving 15 distinct modular CAR T-platforms were analyzed.
• Modular CAR T-platforms demonstrated significant reductions in tumor burden and volume compared to negative controls.
• While no significant difference in tumor burden or volume was observed compared to positive controls, survival probability was higher than negative controls.

Conclusions:

• Modular CAR T-platforms are generally effective in preclinical models.
• These platforms represent a significant and valuable advancement in the field of CAR therapy.
• Further clinical evaluation is warranted based on promising preclinical performance.