Cited by 2,497Cell death mechanisms and regulationToxin Mechanisms and ImmunotoxinsCancer-related Molecular Pathways

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Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo.

Walczak, Henning, Miller, Robert E., Ariail, Kiley, Gliniak, Brian, Griffith, Thomas S., Kubin, Marek, Chin, Wilson, Jones, Jon, Woodward, Anne, Le, Tiep, Smith, Craig, Smolak, Pam, Goodwin, Raymond G., Rauch, Charles T., Schuh, JoAnn C.L., Lynch, David H.·1999·Nature Medicine

DOI 10.1038/5517

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Abstract

To evaluate the utility of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic, we created leucine zipper (LZ) forms of human (hu) and murine (mu) TRAIL to promote and stabilize the formation of trimers. Both were biologically active, inducing apoptosis of both human and murine target cells in vitro with similar specific activities. In contrast to the fulminant hepatotoxicity of LZ-huCD95L in vivo, administration of either LZ-huTRAIL or LZ-muTRAIL did not seem toxic to normal tissues of mice. Finally, repeated treatments with LZ-huTRAIL actively suppressed growth of the TRAIL-sensitive human mammary adenocarcinoma cell line MDA-231 in CB.17 (SCID) mice, and histologic examination of tumors from SCID mice treated with LZ-huTRAIL demonstrated clear areas of apoptotic necrosis within 9-12 hours of injection.

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Authors: Walczak, H., Miller, R. E., Ariail, K., Gliniak, B., Griffith, T. S., Kubin, M., Chin, W., Jones, J., Woodward, A., Le, T., Smith, C., Smolak, P., Goodwin, R. G., Rauch, C. T., Schuh, J. C. L., & Lynch, D. H.
Corresponding author: Lynch, David H.
ORCID: Walczak, Henning
Miller, Robert E.
Griffith, Thomas S.
Smith, Craig
Schuh, JoAnn C.L.
Lynch, David H.
Venue: Nature Medicine
Publisher: Springer Science and Business Media LLC
Published: 1999-02
Volume: 5
Issue: 2
Pages: 157-163
ISSN: 1078-8956 (ISSN-L)
1546-170X
DOI: 10.1038/5517
OpenAlex: W1484817497
Cited by: 2,497
References: 48
Citations by year: 2026: 20 · 2025: 24 · 2024: 33 · 2023: 58 · 2022: 47 · 2021: 57 · 2020: 57 · 2019: 63 · 2018: 64 · 2017: 73 · 2016: 76 · 2015: 80 · 2014: 84 · 2013: 94 · 2012: 96
FWCI: 41.34
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords: TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, leucine zipper, Fas ligand, apoptosis, tumor growth inhibition, hepatotoxicity, SCID mice, TNF receptor, cancer therapy
MeSH terms: Animals, Antineoplastic Agents, Dose-Response Relationship, Drug, Humans, Membrane Glycoproteins, Mice, Inbred BALB C, Mice, Inbred C57BL, Protein Conformation, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Mice, SCID, Apoptosis, Apoptosis Regulatory Proteins, Mice, TNF-Related Apoptosis-Inducing Ligand, Fas Ligand Protein

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Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo.

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