ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
First-in-Human Phase I Trial of a Tumor-Targeted Cytokine (NHS-IL12) in Subjects with Metastatic Solid Tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
113 citing papers in PubMed, 2 syntheses or guidelines pooled it, 168 citations in OpenAlex.
- Engineering cytokines for cancer immunotherapy: a systematic review.Frontiers in immunology · 2023Pooled it
- Development of humanized mouse with patient-derived xenografts for cancer immunotherapy studies: A comprehensive review.Cancer science · 2021Pooled it
- A Phase II Study of Docetaxel and Pembrolizumab plus Interleukin 12 Gene Therapy in Nonmetastatic, Anthracycline-Refractory Triple-Negative Breast Cancer (INTEGRAL).Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Phase II Trial of Interleukin-12 Followed by Interferon Alfa-2b in Patients with Metastatic Malignant Melanoma: Results from CALGB 500001 (Alliance).Cancer immunology research · 2026Trial
- The quadruple immunotherapy for colorectal cancer (QuICC) trial for mismatch repair-proficient metastatic colorectal cancer.The oncologist · 2026Trial
- A phase I trial of SON-1010, a tumor-targeted, interleukin-12-linked, albumin-binding cytokine, shows favorable pharmacokinetics, pharmacodynamics, and safety in healthy volunteers.Frontiers in immunology · 2024Trial
- Clinical and immunologic impact of short-course enzalutamide alone and with immunotherapy in non-metastatic castration sensitive prostate cancer.Journal for immunotherapy of cancer · 2021Trial
- Cytokine fusion proteins for solid tumor therapy: mechanistic insights and clinical advances.Journal of hematology & oncology · 2026Review
- Challenges and opportunities in combining radiotherapy and immunotherapy for localized pancreatic cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- Enhanced efficacy of a next-generation EEEV self-replicating RNA platform for combination cancer immunotherapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Article
- Tumor-Targeted IL-12 (PDS01ADC) with Hepatic Artery Infusion Pump Therapy for Colorectal Liver Metastases: Interim Analysis of a Non-randomized Phase II Trial.JCO oncology advances · 2026Article
- Therapeutic application of IL-12 for cancer therapy.Translational cancer research · 2026Review
- Cytokine delivery and targeting strategies in pet dogs with cancer: a comparative immuno-oncology approach.Frontiers in immunology · 2026Review
- Targeting IL-12 for pancreatic cancer immunotherapy: advances in delivery strategies and clinical translation.Frontiers in immunology · 2026Review
- Review
- Immunocytokines in cancer: a safety perspective.Frontiers in immunology · 2026Review
- TIME for Endometrial Cancer: Advancements and Challenges in Therapeutic Targets for the Endometrial Cancer Tumor Immune Microenvironment.Cancer immunology research · 2025Review
- Protein engineering to overcome limitations of key cytokines in cancer immunotherapy: current approaches and future perspectives.Immuno-oncology technology · 2025Review
- Increased Peripheral T Stem Cell-like Memory Features in Patients with Advanced Solid Tumors Treated with Tumor-Targeting IL-12 Immunocytokine Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe NHS-IL12 immunocytokine is composed of two IL12 heterodimers fused to the NHS76 antibody. Preclinical studies have shown that this antibody targets IL12 to regions of tumor necrosis by binding histones on free DNA fragments in these areas, resulting in enhanced antitumor activity. The objectives of this phase I study were to determine the maximum tolerated dose (MTD) and pharmacokinetics of NHS-IL12 in subjects with advanced solid tumors. PATIENTS AND
methodsSubjects (
resultsThe most frequently observed treatment-related adverse events (TRAE) included decreased circulating lymphocytes, increased liver transaminases, and flu-like symptoms. Of the grade ≥3 TRAEs, all were transient and only one was symptomatic (hyperhidrosis). The MTD is 16.8 μg/kg. A time-dependent rise in IFNγ and an associated rise in IL10 were observed following NHS-IL12. Of peripheral immune cell subsets evaluated, most noticeable were increases in frequencies of activated and mature natural killer (NK) cells and NKT cells. Based on T-cell receptor sequencing analysis, increases in T-cell receptor diversity and tumor-infiltrating lymphocyte density were observed after treatment where both biopsies and peripheral blood mononuclear cells were available. Although no objective tumor responses were observed, 5 subjects had durable stable disease (range, 6-30+ months).
conclusionsNHS-IL12 was well tolerated up to a dose of 16.8 μg/kg, which is the recommended phase II dose. Early clinical immune-related activity warrants further studies, including combination with immune checkpoint inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.