Strategies for clinical dose optimization of T cell-engaging therapies in oncology

Area of Science:

• Immunology
• Pharmacology
• Oncology

Background:

• T cell-engaging (TCE) molecules represent a promising cancer immunotherapy approach by creating synthetic immune synapses.
• The efficacy and toxicity of TCEs are closely linked to drug exposure, presenting challenges in dose regimen design.
• Narrow therapeutic windows necessitate careful optimization to mitigate side effects like cytokine release syndrome and neurotoxicity.

Approach:

• This review evaluates current preclinical and clinical dose optimization strategies for TCEs.
• It highlights quantitative methods for understanding dose-exposure-response relationships.
• Perspectives for improving these strategies and guiding next-generation TCE development are discussed.

Key Points:

• Designing optimal clinical dose regimens for TCEs is complex due to their mechanism of action and narrow therapeutic windows.
• Mitigating side effects such as cytokine release syndrome, neurotoxicity, and on-target off-tumor toxicities is a primary focus.
• Quantitative approaches are essential for understanding and optimizing dose-exposure-response relationships.

Conclusions:

• Effective dose optimization is critical for maximizing the therapeutic benefit of TCE immunotherapies.
• Further development of quantitative strategies will aid in rational design of future TCE molecules and personalized dosing.
• Improved dose regimens are key to enhancing patient outcomes in cancer treatment with TCEs.