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Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells

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CD137 in cancer therapy - bench to bedside.

Kathrine S Rallis^1,2, Jessica J Liegel³, Alexandra Pommier¹

¹Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

|July 10, 2026

Summary

CD137 (4-1BB) is a promising target in cancer immunotherapy, enhancing T-cell responses. While clinical trials show potential, challenges like toxicity and patient variability require further research for optimized therapeutic design.

Keywords:

CD137 bispecifics cancer immunotherapy monoclonal antibodies

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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.