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Isolation and Expansion of Cytotoxic Cytokine-induced Killer T Cells for Cancer Treatment
Published on: January 24, 2020
Harnessing cytokines and chemokines for cancer therapy
David J Propper1, Frances R Balkwill2
1Centre for the Tumour Microenvironment, Barts Cancer Institute, Queen Mary University of London, London, UK.
Abstract:
During the past 40 years, cytokines and cytokine receptors have been extensively investigated as either cancer targets or cancer treatments. A strong preclinical rationale supports therapeutic strategies to enhance the growth inhibitory and immunostimulatory effects of interferons and interleukins, including IL-2, IL-7, IL-12 and IL-15, or to inhibit the inflammatory and tumour-promoting actions of cytokines such as TNF, IL-1β and IL-6. This rationale is underscored by the discovery of altered and dysregulated cytokine expression in all human cancers. These findings prompted clinical trials of several cytokines or cytokine antagonists, revealing relevant biological activity but limited therapeutic efficacy. However, most trials involved patients with advanced-stage disease, which might not be the optimal setting for cytokine-based therapy. The advent of more effective immunotherapies and an increased understanding of the tumour microenvironment have presented new approaches to harnessing cytokine networks in the treatment of cancer, which include using cytokine-based therapies to enhance the activity or alleviate the immune-related toxicities of other treatments as well as to target early stage cancers. Many challenges remain, especially concerning delivery methods, context dependencies, and the pleiotropic, redundant and often conflicting actions of many cytokines. Herein, we discuss the lessons learnt from the initial trials of single-agent cytokine-based therapies and subsequent efforts to better exploit such agents for the treatment of solid tumours.
Insights
Cytokines show promise in cancer therapy, but early trials had limited success. New strategies aim to improve efficacy by targeting early-stage cancers and enhancing other treatments.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Cytokines and their receptors are key players in cancer, with altered expression observed in all human cancers.
- Preclinical data support using cytokines like interferons and interleukins to inhibit tumor growth and boost immunity, or blocking inflammatory cytokines like TNF, IL-1β, and IL-6.
- Past clinical trials of cytokine-based therapies showed biological activity but limited efficacy, often in advanced-stage patients.
Purpose of the Study:
- To review lessons learned from early cytokine-based cancer therapies.
- To explore novel strategies for harnessing cytokine networks in cancer treatment.
- To discuss challenges and future directions for cytokine-based solid tumor therapies.
Main Methods:
- Review of preclinical rationale and clinical trial data for cytokine-based cancer therapies.
- Analysis of the role of cytokines in the tumor microenvironment.
- Discussion of emerging approaches, including combination therapies and targeting early-stage cancers.
Main Results:
- Initial cytokine therapies demonstrated biological activity but limited therapeutic efficacy, particularly in advanced cancers.
- Understanding of the tumor microenvironment and advancements in immunotherapy offer new avenues for cytokine application.
- Challenges persist regarding cytokine delivery, context dependency, and managing pleiotropic effects.
Conclusions:
- Cytokine-based therapies hold potential for cancer treatment, but require refined strategies for optimal efficacy.
- Future research should focus on improved delivery methods, combination therapies, and targeting specific cancer stages.
- Harnessing cytokine networks effectively is crucial for advancing solid tumor treatment.
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