The DOI matches its Crossref record.
Clinical Trials: IL-12 Deaths: Explanation and a Puzzle
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cited by
Sorted by citations
Items 301–333 of 333
Modulating Proliferation, Migration and Differentiation of Mesenchymal Stem Cells Using Interleukins
Srinivasan, S., & Ghone, N. V. (2024) · Current Stem Cell Research & Therapy · doi:10.2174/011574888x313750240524115446 · Cited by 1
Combination of Chemotherapy and Cytokine Therapy in Treatment of Cancers
Malvicini, M., & Mazzolini, G. D. (2020) · Springer eBooks · doi:10.1007/978-3-030-50287-4_10 · Cited by 2
Therapeutic Gene Therapy for Cancer with Interleukin-23
Reay, J. C. (2010) · D-Scholarship@Pitt (University of Pittsburgh) · Cited by 1
18 Mesenchymal stem cells as a carrier for tumor-targeting therapeutics
Chang, A. I., Nolta, J. A., & Wu, J. (2013) · De Gruyter eBooks · doi:10.1515/9783110298307.353 · Cited by 1
Cao, X., Collins, L. I., Cai, S. F., et al. (2008) · Blood · doi:10.1182/blood.v112.11.2558.2558 · Cited by 1
Host Defense Mechanisms Against Viruses
Lewis, D. B. (2004) · Elsevier eBooks · doi:10.1016/b978-0-7216-9654-6.50156-9 · Cited by 1
Drugs acting on the immune system
Vial, T., & Descotes, J. (1997) · Side effects of drugs annual · doi:10.1016/s0378-6080(05)80399-x · Cited by 1
Cytokines as Mediators of Lung Innate Immunity
Standiford, T. J., Merhad, B., & Tsai, W. C. (2002) · Springer eBooks · doi:10.1007/978-3-642-57210-4_9 · Cited by 1
Interleukin-12: Biology and Clinical Studies
Aulitzky, W. E., & Huber, C. G. (1997) · Springer eBooks · doi:10.1007/978-3-642-60562-8_10
Shibata, M., Morimoto, J., Shibata, E., et al. (2011) · InTech eBooks · doi:10.5772/30904
“However, despite initial enthusiasm for recombinant IL-12 as a potential anti-tumor agent, severe systemic toxicities have repeatedly been reported in clinical trials, limiting its use [43,44].”
BackgroundZaharoff, D. A., Heffernan, M. J., Fallon, J. K., et al. (2012) · doi:10.1002/9781119962977.ch27
Adenovirus cancer gene therapy
Powell, M. B., & Wilkinson, G. W. G. (2001) · Perspectives in medical virology · doi:10.1016/s0168-7069(01)05016-9
Hanagiri, T., Imahayashi, S., Yoshino, I., et al. (2000) · International Journal of Clinical Oncology · doi:10.1007/pl00012047
“A phase II clinical trial of IL-12 in patients with advanced renal cell carcinoma was discontinued because of severe toxicity, including death.(7) Therefore, sophisticated experimental models are required to re-evaluate the efficacy of IL-12 therapy on solid tumors in humans.”
BackgroundHuang, J. (2005) · D-Scholarship@Pitt (University of Pittsburgh)
Clinical and biological effects of interleukin 12 in patients with renal cell carcinoma
Portielje, J. E. A. (2002) · RePub (Erasmus University Rotterdam)
Talmadge, J. E. (2003) · Elsevier eBooks · doi:10.1016/b978-012688721-1/50011-8
Novel Cytokines for Immunotherapy of Melanoma
Bhatia, S., & Thompson, J. A. (2011) · Springer eBooks · doi:10.1007/978-1-61779-407-0_17
Chitosan Decontamination with Non-Thermal Nitrogen Plasma to Enable Internal Use
Crofton, A. R. (2016) · The Scholars Repository - LLU (Loma Linda University)
Computer languages in pharmaceutical design
Robson, B. (1997) · Springer eBooks · doi:10.1007/978-94-017-1120-3_19
Mesenchymal Stem Cells as a Carrier for Targeting Anti-Tumor Therapeutics
Wu, J. (2013) · eScholarship (California Digital Library)
Algazi, A. P., Twitty, C., Tsai, K. K., Le, M. H., Pierce, R. H., Campbell, J. S., Browning, E., Hermiz, R., Canton, D., Bannavong, D., et al. (2019) · SSRN Electronic Journal · doi:10.2139/ssrn.3346978
Lokale Gentherapie zur Behandlung von Lebertumoren
Schmitz, V., & Caselmann, W. H. (2003) · Springer eBooks · doi:10.1007/978-3-642-55839-9_28
Nelles, M. E., Salerno, V., Xu, Y., et al. (2010) · Humana Press eBooks · doi:10.1007/978-1-60761-980-2_13
Immune dysregulation and CD4+ T cell loss in HIV-1 infection
Meyaard, L., & Miedema, F. F. (1997) · Springer eBooks · doi:10.1007/978-3-642-60867-4_4
(2015) · Elsevier eBooks · doi:10.1016/b978-0-444-53717-1.00906-9
Interleukin-12 toxicity mystery solved
&NA; (1995) · Reactions Weekly · doi:10.2165/00128415-199505800-00002
Kaufman, H. L., & Dharmadhikari, N. (2017) · Springer eBooks · doi:10.1007/978-1-4419-0717-2_144
Kasahara, S., Kashiwagi, M., Inubushi, T., Sugauchi, A., Deyong, W., Kurioka, K., Miyagawa, K., Matsuda, T., Seki, S., Kogo, M., et al. (2026) · Oral Diseases · doi:10.1111/odi.70399
Ishikawa, M., Nambiar, D. K., Sastri, J., Bowling, F., Ishimoto, K., Tao, F., Takahashi, K., Stephanek, I., Cao, H., Leitner, D., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.07.666585
Interleukin-12 Gene Therapy for Cancer Immunotherapy
Jesenko, T., Tratar, U. L., Serša, G., et al. (2026) · Cancer drug discovery and develogment/Cancer drug discovery and development · doi:10.1007/978-3-032-24071-2_12
Combination of Chemotherapy and Cytokine Therapy in Treatment of Cancers
Malvicini, M., Rizzo, M., Alaniz, L. D., et al. (2014) · Springer eBooks · doi:10.1007/978-3-662-44946-2_11
Metadata
- Authors
- Cohen, J.
- Corresponding author
- Cohen, J.
- Venue
- Science
- Published
- 1995-11-10
- Volume
- 270
- Issue
- 5238
- Pages
- 908a-908
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
