Antibody-Cytokine Fusion Proteins for Treatment of Cancer: Engineering Cytokines for Improved Efficacy and Safety
Open accessAbstract
The true potential of cytokine therapies in cancer treatment is limited by the inability to deliver optimal concentrations into tumor sites due to dose-limiting systemic toxicities. To maximize the efficacy of cytokine therapy, recombinant antibody-cytokine fusion proteins have been constructed by a number of groups to harness the tumor-targeting ability of monoclonal antibodies. The aim is to guide cytokines specifically to tumor sites where they might stimulate more optimal anti-tumor immune responses while avoiding the systemic toxicities of free cytokine therapy. Antibody-cytokine fusion proteins containing interleukin (IL)-2, IL-12, IL-21, tumor necrosis factor (TNF)α, and interferons (IFNs) α, β, and γ have been constructed and have shown anti-tumor activity in preclinical and early-phase clinical studies. Future priorities for development of this technology include optimization of tumor targeting, bioactivity of the fused cytokine, and choice of appropriate agents for combination therapies. This review is intended to serve as a framework for engineering an ideal antibody-cytokine fusion protein, focusing on previously developed constructs and their clinical trial results.
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Combining a monoclonal antibody with a therapeutic radionuclide allows targeted destruction of lymphoma cells, enhancing treatment outcomes and minimizing systemic toxicity.
“Combining a monoclonal antibody with a therapeutic radionuclide allows targeted destruction of lymphoma cells, enhancing treatment outcomes and minimizing systemic toxicity [95].”
From Radiopharmaceuticals: navigating the frontier of precision medicine and therapeutic innovation (2024) · cites this paper as [95]
The “Exploiting Antibodies for Cytokine Delivery” section (page unavailable) says radionuclides can be attached to antibodies for tumor-specific targeting, and identifies CD20 on B-cell lymphomas as an antibody target. It does not report that antibody–radionuclide treatment improves lymphoma outcomes or minimizes systemic toxicity; the improved outcomes described in the IL-2 Fusion Proteins section concern rituximab, not a radionuclide conjugate. (LLM, conf=0.86)
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Cytokines in Cancer Immunotherapy
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“Combining a monoclonal antibody with a therapeutic radionuclide allows targeted destruction of lymphoma cells, enhancing treatment outcomes and minimizing systemic toxicity [95].”
BackgroundImmunocytokines are a promising immunotherapeutic approach against glioblastoma
Weiss, T., Puca, E., Silginer, M., Hemmerle, T., Pazahr, S., Bink, A., Weller, M., Neri, D., & Roth, P. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.abb2311 · Cited by 133 · see citing works
- Authors
- Young, P. A., Morrison, S. L., & Timmerman, J. M.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Timmerman, John M.
- Venue
- Seminars in Oncology
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 41
- Issue
- 5
- Pages
- 623-636
- ISSN
- 0093-7754 (ISSN-L)
- PMC
- PMC4354941
- OpenAlex
- W2111785254
- Cited by
- 66
- References
- 69
- Citations by year
- 2025: 5 · 2024: 7 · 2023: 6 · 2022: 5 · 2021: 9 · 2020: 6 · 2019: 4 · 2018: 7 · 2017: 8 · 2016: 9
- FWCI
- 4.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Seminars in Oncology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T32HL066992)
- National Cancer Institute (R01CA162964)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- antibody-cytokine fusion proteins, cytokine therapy, cancer immunotherapy, tumor targeting, interleukin-2, IL-12, IL-21, TNF-α, interferon, systemic toxicity, antitumor immunity, combination therapy, clinical trials
- MeSH terms
- Animals, Antibodies, Monoclonal, Humans, Immunotherapy, Neoplasms, Recombinant Fusion Proteins, Safety, Protein Engineering, Cytokines
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