CD137 in cancer therapy - bench to bedside

Area of Science:

• Immunology
• Cancer Immunotherapy
• Molecular Biology

Background:

• CD137 (4-1BB; TNFRSF9) is a costimulatory receptor on immune cells, crucial for T-cell survival and expansion.
• Its role in reinforcing T-cell functions makes it an attractive target for cancer immunotherapy.

Purpose of the Study:

• To review CD137 biology, emerging therapeutic strategies, and translational and clinical directions.
• To summarize the current understanding and future prospects of CD137 as an immunologic target in cancer therapy.

Main Methods:

• Review of existing literature on CD137 biology and therapeutic applications.
• Analysis of clinical trial data and non-human primate models for CD137 agonists.
• Discussion of innovative approaches like bioreactor systems, CD137L co-culture, and single-cell technologies.

Main Results:

• CD137 agonists have demonstrated anti-tumor activity in clinical trials.
• Hepatotoxicity and variable patient responses are significant challenges associated with CD137 agonists.
• CD137 signaling modulates alloreactivity, impacting graft-versus-host disease.

Conclusions:

• Despite challenges like toxicity and resistance, CD137 remains a compelling target in cancer immunotherapy.
• Future research should focus on context-specific agonism, cellular engineering, and multi-omic integration for improved patient selection and therapeutic design.