Micromolar affinity CAR T cells to ICAM-1 achieves rapid tumor elimination while avoiding systemic toxicity

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Chimeric antigen receptor (CAR) T cell therapy shows success in hematological cancers.
• Challenges remain for solid tumors due to safety concerns and efficacy limitations.

Purpose of the Study:

• To engineer affinity-variant CAR T cells targeting ICAM-1 for improved solid tumor treatment.
• To evaluate the impact of CAR affinity on anti-tumor efficacy and safety.

Main Methods:

• Constructed affinity-variant CARs targeting ICAM-1 via its ligand LFA-1.
• Assessed T cell potency in vitro against varying ICAM-1 densities.
• Utilized a solid tumor mouse model for in vivo efficacy and toxicity assessment.
• Employed PET/CT for longitudinal T cell tracking and cytokine measurement.

Main Results:

• In vitro T cell potency correlated directly with CAR affinity and ICAM-1 expression levels.
• Micromolar affinity CAR T cells demonstrated superior anti-tumor efficacy and safety in vivo.
• Longitudinal tracking revealed enhanced expansion and contraction kinetics for micromolar affinity CAR T cells.

Conclusions:

• Developed ICAM-1-specific CAR T cells with broad anti-tumor applicability.
• Reduced affinity targeting strategy significantly enhances CAR T cell efficacy and safety for solid tumors.