ArticleOncoimmunology2020
Identification and characterization of M6903, an antagonistic anti-TIM-3 monoclonal antibody.
Article in Oncoimmunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review.Cell communication and signaling : CCS · 2021Pooled it
- Blockade of co-inhibitory receptor immune checkpoint protein TIM3/CD366 augments the anti-cancer activity of CAR-T therapy in solid tumors: An ovarian cancer example.Genes & diseases · 2026Article
- Review
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Decoding the gut microbiota-immune dialogue: from bidirectional axis to therapeutic applications.Journal of nanobiotechnology · 2026Review
- Galectin-9-An Emerging Glyco-Immune Checkpoint Target for Cancer Therapy.International journal of molecular sciences · 2025Review
- TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives.Molecular biomedicine · 2025Review
- AI-enhanced profiling of phage-display-identified anti-TIM3 and anti-TIGIT novel antibodies.Frontiers in immunology · 2025Article
- Structural aspects of CEACAM1 interactions.European journal of clinical investigation · 2024Review
- Small molecules from antibody pharmacophores (SMAbPs) as a hit identification workflow for immune checkpoints.Science advances · 2024Article
- High-dimensional mapping of human CEACAM1 expression on immune cells and association with melanoma drug resistance.Communications medicine · 2024Article
- Structure-Based Rational Design of Constrained Peptides as TIM-3 Inhibitors.ACS medicinal chemistry letters · 2024Article
- Article
- Discovery of lung adenocarcinoma tumor antigens and ferroptosis subtypes for developing mRNA vaccines.Scientific reports · 2024Article
- Galectin-9 - ligand axis: an emerging therapeutic target for multiple myeloma.Frontiers in immunology · 2024Review
- TIM proteins and microRNAs: distinct impact and promising interactions on transplantation immunity.Frontiers in immunology · 2024Review
- A new emerging target in cancer immunotherapy: Galectin-9 (LGALS9).Genes & diseases · 2023Review
- Current Approaches of Immune Checkpoint Therapy in Chronic Lymphocytic Leukemia.Current treatment options in oncology · 2023Review
- Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy.Journal of hematology & oncology · 2023Review
- Highly reliable GIGA-sized synthetic human therapeutic antibody library construction.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
19 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cell immunoglobulin and mucin domain-3 (TIM-3) is an immune checkpoint that regulates normal immune responses but can be exploited by tumor cells to evade immune surveillance. TIM-3 is primarily expressed on immune cells, particularly on dysfunctional and exhausted T cells, and engagement of TIM-3 with its ligands promotes TIM-3-mediated T cell inhibition. Antagonistic ligand-blocking anti-TIM-3 antibodies have the potential to abrogate T cell inhibition, activate antigen-specific T cells, and enhance anti-tumor immunity. Here we describe M6903, a fully human anti-TIM-3 antibody without effector function and with high affinity and selectivity to TIM-3. We demonstrate that M6903 blocks the binding of TIM-3 to three of its ligands, phosphatidylserine (PtdSer), carcinoembryonic antigen cell adhesion-related molecule 1 (CEACAM1), and galectin 9 (Gal-9). These results are supported by an atomic resolution crystal structure and functional assays, which demonstrate that M6903 monotherapy enhanced T cell activation. This activation was further enhanced by the combination of M6903 with bintrafusp alfa, a bifunctional fusion protein that simultaneously blocks the transforming growth factor-β (TGF-β) and programmed death ligand 1 (PD-L1) pathways. M6903 and bintrafusp alfa combination therapy also enhanced anti-tumor efficacy in huTIM-3 knock-in mice, relative to either monotherapy. These in vitro and in vivo data, along with favorable pharmacokinetics in marmoset monkeys, suggest that M6903 as a monotherapy warrants further pre-clinical assessment and that M6903 and bintrafusp alfa may be a promising combination therapy in the clinic.
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