ArticleJournal for immunotherapy of cancer2023
CLN-978, a novel half-life extended CD19/CD3/HSA-specific T cell-engaging antibody construct with potent activity against B-cell malignancies with low CD19 expression.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- T cell engagers in autoimmune diseases.Nature reviews. Immunology · 2026Review
- TCR-mimic bispecific nanobody-based T cell engager targeting intracellular tumor antigens for cancer immunotherapy.Signal transduction and targeted therapy · 2026Article
- Can we cure autoimmunity?Current opinion in immunology · 2026Review
- Next-generation T cell engagers for cancer and autoimmune diseases.Frontiers in immunology · 2026Review
- Predicting the Pharmacokinetics of T-Cell Engagers as a Function of Target-Mediated Drug Disposition.Clinical and translational science · 2025Article
- Topical delivery of a human single-domain antibody targeting IL-33 to inhibit mucosal inflammation.Cellular & molecular immunology · 2025Article
- Advances in Targeted Therapy for Systemic Lupus Erythematosus: Current Treatments and Novel Approaches.International journal of molecular sciences · 2025Review
- Mechanistic insights into resistance mechanisms to T cell engagers.Frontiers in immunology · 2025Review
- The Evolving Applications of Bispecific Antibodies: Reaping the Harvest of Early Sowing and Planting New Seeds.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Current use and development of monoclonal antibodies for the treatment of systemic lupus erythematosus: a review.Antibody therapeutics · 2025Review
- CD19-directed T cell-engaging antibodies for the treatment of autoimmune disease.The Journal of experimental medicine · 2024Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite significant progress in the development of T cell-engaging therapies for various B-cell malignancies, a high medical need remains for the refractory disease setting, often characterized by suboptimal target levels.
methodsTo address this issue, we have developed a 65-kDa multispecific antibody construct, CLN-978, with affinities tuned to optimize the killing of low-CD19 expressing tumor cells. CLN-978 bound to CD19 on B cells with picomolar affinity, and to CD3ε on T cells with nanomolar affinity. A serum albumin binding domain was incorporated to extend serum half-life. In this setting, we biophysically characterize and report the activities of CLN-978 in cell co-culture assays, multiple mouse models and non-human primates.
resultsHuman T cells redirected by CLN-978 could eliminate target cells expressing less than 300 copies of CD19 on their surface. The half-life extension and high affinity for CD19 led to significant antitumor activity in murine lymphoma models at very low doses of CLN-978. In primates, we observed a long serum half-life, deep and sustained depletion of normal B cells, and remarkable tolerability, in particular, reduced cytokine release when CLN-978 was administered subcutaneously.
conclusionsCLN-978 warrants further exploration. An ongoing clinical phase 1 trial is investigating safety, pharmacokinetics, pharmacodynamics, and the initial therapeutic potential of subcutaneously administered CLN-978 in patients with non-Hodgkin's lymphoma.
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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.