Landscape of T-cell engagers in solid tumors

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• T-cell engagers (TCEs) are bispecific/multispecific molecules activating T cells against tumor antigens.
• TCEs are effective in blood cancers but face challenges in solid tumors.
• Recent successes with tebentafusp and tarlatamab validate TCEs for solid tumors, with expanding targets like STEAP1, MUC16, and PRAME.

Purpose of the Study:

• To review recent advances in T-cell engagers (TCEs) for solid tumor treatment.
• To discuss strategies for overcoming challenges in solid tumor immunotherapy.
• To highlight next-generation TCE engineering and combination approaches.

Main Methods:

• Review of recent scientific literature on T-cell engagers in solid tumors.
• Analysis of engineering strategies to enhance TCE efficacy and safety.
• Examination of combination regimens involving TCEs.

Main Results:

• Next-generation TCEs employ strategies like half-life extension and masking for improved intratumoral activity and reduced toxicity.
• Combination therapies with checkpoint inhibitors, chemotherapy, and other platforms are being investigated to enhance response durability.
• Rational target selection, context-dependent activation, and biomarkers are key for patient stratification.

Conclusions:

• Next-generation TCEs are being engineered to overcome solid tumor-specific challenges.
• Combination strategies are crucial for improving TCE efficacy and overcoming immune resistance.
• Biomarker-driven patient stratification will be essential for broadening TCE application in solid tumors.