Clinical Trials: IL-12 Deaths: Explanation and a Puzzle

Cohen, J.

doi:10.1126/science.270.5238.908a

Cited by 333Immunotoxicology and immune responsesImmunotherapy and Immune ResponsesPharmacovigilance and Adverse Drug Reactions

Clinical Trials: IL-12 Deaths: Explanation and a Puzzle

Cohen, J.·1995·Science

DOI 10.1126/science.270.5238.908a

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Abstract

Researchers investigating toxic reactions that killed two patients in a trial of interleukin-12 earlier this year have reached a surprising conclusion: The drug is highly toxic if it is given in multiple high doses, but those effects can be avoided if the multiple doses are preceded by a single dose followed by a rest period. The initial dose apparently imprints a memory on the immune system, but the mechanism is unclear.

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Crossref · 10.1126/science.270.5238.908a

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The administration of recombinant cytokines (e.g., interleukin-1, interleukin-6, interleukin-12, interleukin-18, tumor necrosis factor, and interferon-γ) in animal models and for cancer treatment in humans induces severe toxic effects or lethality consistent with the central role of cytokines as mediators of hyperinflammation in cytokine storm.
“The administration of recombinant cytokines (e.g., interleukin-1, interleukin-6, interleukin-12, interleukin-18, tumor necrosis factor [TNF], and interferon-γ) in animal models and for cancer treatment in humans induces severe toxic effects or lethality consistent with the central role of cytokines as mediators of hyperinflammation in cytokine storm.”
From Cytokine storm (2020) · cites this paper as [28]

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Authors: Cohen, J.
Corresponding author: Cohen, J.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1995-11-10
Volume: 270
Issue: 5238
Pages: 908a-908
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.270.5238.908a
OpenAlex: W1609710757
Cited by: 332
References: 0
Citations by year: 2026: 2 · 2025: 8 · 2024: 15 · 2023: 11 · 2022: 13 · 2021: 11 · 2020: 16 · 2019: 15 · 2018: 8 · 2017: 9 · 2016: 15 · 2015: 8 · 2014: 5 · 2013: 13 · 2012: 15
FWCI: 2.44
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Keywords: IL-12, drug toxicity, dose scheduling, immunological memory, cytokine therapy
MeSH terms: Animals, Carcinoma, Renal Cell, Clinical Trials as Topic, Drug Administration Schedule, Humans, Kidney Neoplasms, Macaca fascicularis, Recombinant Proteins, United States, United States Food and Drug Administration, Multicenter Studies as Topic, Th1 Cells, Th2 Cells, Interleukin-12, Mice

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Clinical Trials: IL-12 Deaths: Explanation and a Puzzle

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