Targeting tumor-necrosis factor receptor pathways for tumor immunotherapy
David A Schaer1,2, Daniel Hirschhorn-Cymerman1, Jedd D Wolchok1,3,4,5
1Swim Across America Laboratory, Immunology Program, Sloan-Kettering Institute for Cancer Research, New York, NY 10065, USA.
Journal for Immunotherapy of Cancer
|May 24, 2014
Summary
Tumor immunotherapy is advancing with new targets like the tumor necrosis factor receptor (TNFR) family. These co-stimulatory molecules show promise in enhancing immune responses against cancer.
Area of Science:
- Immunology and Oncology
- Molecular Biology
Background:
- The success of ipilimumab and programmed death-1 (PD-1) pathway inhibitors has accelerated tumor immunotherapy research.
- New therapeutic targets within the tumor necrosis factor receptor (TNFR) superfamily are emerging for cancer treatment.
Purpose of the Study:
- To review the immune response to tumors.
- To summarize preclinical and early clinical data for select TNFR family members as cancer therapies.
- To discuss translational challenges and potential combination strategies for durable antitumor responses.
Main Methods:
- Review of existing literature on tumor immunology and TNFR family members.
- Analysis of in vitro and in vivo preclinical data.
- Examination of early-stage clinical trial findings for TNFR-targeted agents.
Main Results:
- Agonist antibodies targeting co-stimulatory TNFR molecules modulate T-cell activation and enhance immune responses.
- Specific TNFR family members like 4-1BB, OX40, GITR, HVEM, and CD27 are under investigation.
- Preclinical data support the development of these agents for various cancers.
Conclusions:
- Select TNFR family members represent promising targets for novel cancer immunotherapies.
- Overcoming translational challenges and exploring combination therapies are crucial for clinical success.
- The goal is to induce robust and lasting antitumor immune responses.
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