ArticleJournal of hematology & oncology2023
Development and characterization of NILK-2301, a novel CEACAM5xCD3 κλ bispecific antibody for immunotherapy of CEACAM5-expressing cancers.
Article in Journal of hematology & oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Review
- Dual-recognizing antibodies targeting CEACAMs in the tumor microenvironment: towards more precise targeting.Cell communication and signaling : CCS · 2026Review
- Clinical applications of antibody-drug conjugates in advanced non-small cell lung cancer.Frontiers in immunology · 2026Review
- Amide-Linked Local Anesthetics Alter Tumor Biology in a Complex Human Tissue Model of Non-Small Cell Lung Adenocarcinoma.Advanced biology · 2025Article
- Application of humanized mice in the safety experiments of antibody drugs.Animal models and experimental medicine · 2025Review
- Artemisinin derivatives differently affect cell death of lung cancer subtypes by regulating GPX4 in patient-derived tissue cultures.Cell death discovery · 2025Article
- Advances in cancer immunotherapy: historical perspectives, current developments, and future directions.Molecular cancer · 2025Review
- Immunotherapy in Breast Cancer: Beyond Immune Checkpoint Inhibitors.International journal of molecular sciences · 2025Review
- NI-3201 Is a Bispecific Antibody Mediating PD-L1-Dependent CD28 Co-stimulation on T Cells for Enhanced Tumor Control.Cancer immunology research · 2025Article
- In Vitro Evaluation of the Safety and Efficacy ofCancers · 2025Article
- Tumor-dependent myeloid and lymphoid cell recruitment in genO-BRGSF-HIS mice: a novel tool for evaluating immunotherapies.Frontiers in immunology · 2025Article
- Advancements in 3D In Vitro Models for Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Stepping forward: T-cell redirecting bispecific antibodies in cancer therapy.Acta pharmaceutica Sinica. B · 2024Review
- Targeting CEACAM5-positive solid tumors using NILK-2401, a novel CEACAM5xCD47 κλ bispecific antibody.Frontiers in immunology · 2024Article
- Article
Corrections and comments
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Authors and funding
26 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundT-cell retargeting to eliminate CEACAM5-expressing cancer cells via CEACAM5xCD3 bispecific antibodies (BsAbs) showed limited clinical activity so far, mostly due to insufficient T-cell activation, dose-limiting toxicities, and formation of anti-drug antibodies (ADA).
methodsWe present here the generation and preclinical development of NILK-2301, a BsAb composed of a common heavy chain and two different light chains, one kappa and one lambda, determining specificity (so-called κλ body format).
resultsNILK-2301 binds CD3ɛ on T-cells with its lambda light chain arm with an affinity of ≈100 nM, and the CEACAM5 A2 domain on tumor cells by its kappa light chain arm with an affinity of ≈5 nM. FcγR-binding is abrogated by the "LALAPA" mutation (Leu234Ala, Leu235Ala, Pro329Ala). NILK-2301 induced T-cell activation, proliferation, cytokine release, and T-cell dependent cellular cytotoxicity of CEACAM5-positive tumor cell lines (5/5 colorectal, 2/2 gastric, 2/2 lung), e.g., SK-CO-1 (E
conclusionsIn summary, NILK-2301 combines promising preclinical activity and safety with lower probability of ADA-generation due to its format compared to other molecules and is scheduled to enter clinical testing at the end of 2023.
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