ArticlePloS one2016
Targeting Attenuated Interferon-α to Myeloma Cells with a CD38 Antibody Induces Potent Tumor Regression with Reduced Off-Target Activity.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 59 citations in OpenAlex.
- Targeted interferon therapy with modakafusp alfa for relapsed or refractory multiple myeloma.Blood · 2025Trial
- CDCP1-targeted antibody-drug conjugates and immunocytokines for cancer therapy.Cancer chemotherapy and pharmacology · 2026Article
- A modular platform for Sterically Masked Activated Cytokines (SMACks).Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Enhancing the Anticancer Activity of a Carcinoma-Directed Peptide-HLA-I Fusion Protein by Armoring with Mutein IFNα.International journal of molecular sciences · 2025Article
- Accumulation of CD38 in Hybrid Epithelial/Mesenchymal Cells Promotes Immune Remodeling and Metastasis in Breast Cancer.Cancer research · 2025Article
- Vax-Innate: improving therapeutic cancer vaccines by modulating T cells and the tumour microenvironment.Nature reviews. Immunology · 2025Review
- CD38-targeted attenuated interferon alpha immunocytokine activates both innate and adaptive immune cells to drive anti-tumor activity.PloS one · 2025Article
- A phase Ib/II study of modakafusp alfa alone and in combination with pembrolizumab in patients with advanced or metastatic solid tumors.Frontiers in oncology · 2025Article
- Implications of glycosylation for the development of selected cytokines and their derivatives for medical use.Biotechnology advances · 2024Review
- Advancements and challenges in immunocytokines: A new arsenal against cancer.Acta pharmaceutica Sinica. B · 2024Review
- Article
- Pharmacokinetics, pharmacodynamics, and toxicity of a PD-1-targeted IL-15 in cynomolgus monkeys.PloS one · 2024Article
- Tumor-Homing Antibody-Cytokine Fusions for Cancer Therapy.OncoTargets and therapy · 2024Review
- Targeted therapy for multiple myeloma: an overview on CD138-based strategies.Frontiers in oncology · 2024Review
- Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses.Oncogene · 2023Article
- Targeted Cytokine Delivery for Cancer Treatment: Engineering and Biological Effects.Pharmaceutics · 2023Review
- Bioinspired Design of Artificial Signaling Systems.Biochemistry · 2023Review
- Cytokine conjugation to enhance T cell therapy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Emerging principles of cytokine pharmacology and therapeutics.Nature reviews. Drug discovery · 2023Review
- Beyond the cell: novel noncellular immunotherapy approaches to multiple myeloma.Hematology. American Society of Hematology. Education Program · 2022Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interferon-α (IFNα) has been prescribed to effectively treat multiple myeloma (MM) and other malignancies for decades. Its use has waned in recent years, however, due to significant toxicity and a narrow therapeutic index (TI). We sought to improve IFNα's TI by, first, attaching it to an anti-CD38 antibody, thereby directly targeting it to MM cells, and, second, by introducing an attenuating mutation into the IFNα portion of the fusion protein rendering it relatively inactive on normal, CD38 negative cells. This anti-CD38-IFNα(attenuated) immunocytokine, or CD38-Attenukine™, exhibits 10,000-fold increased specificity for CD38 positive cells in vitro compared to native IFNα and, significantly, is ~6,000-fold less toxic to normal bone marrow cells in vitro than native IFNα. Moreover, the attenuating mutation significantly decreases IFNα biomarker activity in cynomolgus macaques indicating that this approach may yield a better safety profile in humans than native IFNα or a non-attenuated IFNα immunocytokine. In human xenograft MM tumor models, anti-CD38-IFNα(attenuated) exerts potent anti-tumor activity in mice, inducing complete tumor regression in most cases. Furthermore, anti-CD38-IFNα(attenuated) is more efficacious than standard MM treatments (lenalidomide, bortezomib, dexamethasone) and exhibits strong synergy with lenalidomide and with bortezomib in xenograft models. Our findings suggest that tumor-targeted attenuated cytokines such as IFNα can promote robust tumor killing while minimizing systemic toxicity.
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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.