ArticleCancer immunology research2024
CLN-617 Retains IL2 and IL12 in Injected Tumors to Drive Robust and Systemic Immune-Mediated Antitumor Activity.
Article in Cancer immunology research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06035744 (A Phase 1 First-in-Human Study to Investigate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamic Activity of CLN-617 Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors), which is not on this map. Cited by 15 papers.
What it found
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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.
A Phase 1 First-in-Human Study to Investigate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamic Activity of CLN-617 Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
Who cites it
15 citing papers in PubMed.
- Collagen-Binding IL-15 Immunocytokine Armed Oncolytic Adenovirus Establishes a Self-Reinforcing Immunostimulatory Milieu to Potentiate Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cytokine fusion proteins for solid tumor therapy: mechanistic insights and clinical advances.Journal of hematology & oncology · 2026Review
- AML-Targeted Metal-Polyphenol Nanoplatform Induces Ferroptosis-ICD Cascade for Antitumor Immunity Boosting.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Immuno-cytotoxic convergence: integrating antibody‒drug conjugates and immunofusion proteins to overcome resistance in gastrointestinal cancers.Journal of hematology & oncology · 2026Review
- Priorities for local immunotherapy research and drug development.Journal for immunotherapy of cancer · 2026Review
- Cytokine delivery and targeting strategies in pet dogs with cancer: a comparative immuno-oncology approach.Frontiers in immunology · 2026Review
- Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor models.Oncoimmunology · 2025Article
- Protein engineering to overcome limitations of key cytokines in cancer immunotherapy: current approaches and future perspectives.Immuno-oncology technology · 2025Review
- Inhibitory pattern recognition receptors: lessons from LAIR1.Nature reviews. Immunology · 2025Review
- In Situ Vaccines in the Era of Cancer Immunotherapy: Conceptual Innovation and Clinical Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Cytokine Therapy in Bladder Cancer: Mechanisms, Efficacy, and Future Prospects.Current issues in molecular biology · 2025Review
- Potentiating intratumoral therapy with immune checkpoint inhibitors: shifting the paradigm of multimodality therapeutics.Immuno-oncology technology · 2025Review
- Intratumoral immunotherapy prior to cancer surgery, a promising therapeutic approach.Frontiers in immunology · 2025Review
- Trifunctional antibody-cytokine fusion protein formats for tumor-targeted combination of IL-15 with IL-7 or IL-21.Frontiers in immunology · 2025Article
- Intratumoral injection and retention hold promise to improve cytokine therapies for cancer.Frontiers in oncology · 2024Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite clinical evidence of antitumor activity, the development of cytokine therapies has been hampered by a narrow therapeutic window and limited response rates. Two cytokines of high interest for clinical development are interleukin 2 (IL2) and interleukin 12 (IL12), which potently synergize to promote the activation and proliferation of T cells and NK cells. However, the only approved human IL2 therapy, Proleukin, is rarely used in the clinic due to systemic toxicities, and no IL12 product has been approved to date due to severe dose-limiting toxicities. Here, we describe CLN-617, a first-in-class therapeutic for intratumoral (IT) injection that co-delivers IL2 and IL12 on a single molecule in a safe and effective manner. CLN-617 is a single-chain fusion protein comprised of IL2, leukocyte-associated immunoglobulin-like receptor 2 (LAIR2), human serum albumin (HSA), and IL12. LAIR2 and HSA function to retain CLN-617 in the treated tumor by binding collagen and increasing molecular weight, respectively. We found that IT administration of a murine surrogate of CLN-617, mCLN-617, eradicated established treated and untreated tumors in syngeneic models, significantly improved response to anti-PD1 checkpoint therapy, and generated a robust abscopal response dependent on cellular immunity and antigen cross-presentation. CLN-617 is being evaluated in a clinical trial in patients with advanced solid tumors (NCT06035744).
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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.