ArticleJournal for immunotherapy of cancer2025
Novel and potent MICA/B antibody is therapeutically effective in
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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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.
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Who cites it
8 citing papers in PubMed.
- Molecular insights and therapeutic implications for the tumor suppressor role of LKB1 in non-small cell lung cancer.Cancer letters · 2026Review
- Comparative analysis of anti-MICA scFv affinities: Insights from three label-free biophysical methods and biological validation.Biotechnology reports (Amsterdam, Netherlands) · 2026Article
- Targeting the MICA/B-NKG2D axis in cancer: from molecular structure to immunotherapeutic strategies-a narrative review.Translational cancer research · 2026Review
- A fully human IgG1 antibody targeting MICA α1 domain inhibits interaction with NKG2D and activates immune effector functions against MICA-expressing cells.Frontiers in immunology · 2026Article
- MICA protein as a plasma biomarker for dermatomyositis with malignancy: a proteome-wide Mendelian randomization and ELISA study.Clinical rheumatology · 2026Article
- Insights into ectodomain shedding as a novel target in natural killer cell-based immunotherapy for cancer.Frontiers in immunology · 2026Review
- Association Between Amino Acid Polymorphisms in MICA and MICA-NKG2D Interaction Affinity: Implications and Significance for Tumor Immunity.Biomolecules · 2025Review
- Targeting LKB1/STK11-mutant cancer: distinct metabolism, microenvironment, and therapeutic resistance.Trends in pharmacological sciences · 2025Review
Corrections and comments
- Update of
Authors and funding
14 authors.
Funding
Abstract
backgroundConcurrent
methodsExpression of NK cell activating ligands in NSCLC cell line and patient data were analyzed. Cell surface expression of MICA/B in NSCLC cell lines was determined through flow cytometry while ligand shedding in both patient blood and cell lines was determined through ELISA. We engineered an antibody-dependent cellular cytotoxicity (ADCC) enhanced MICA/B monoclonal antibody, AHA-1031, which prevents ligand shedding without interfering with binding to natural killer group 2D while targeting cancer cells via superior ADCC. We performed in vitro assays using ELISA and flow cytometry-based assays to confirm that our antibody potently binds to and stabilizes MICA/B expression across lung cancer and other solid tumor cell lines. Additionally, we used two KL mutant NSCLC cell lines and a KL mutant patient-derived xenograft (PDX) model to demonstrate in vivo antitumor efficacy and flow cytometry analysis for immune cell activation profiling.
resultsNSCLC cell lines exhibit high MICA/B expression and secrete soluble MICA/B in vitro. Soluble MICA/B is also detected in patient blood samples. AHA-1031 binds to the α3 domain of MICA/B, preventing shedding and targeting tumor cells to ADCC. AHA-1031 exhibits high affinity and specificity to MICA/B, preventing MICA/B shedding in tumor lines and inducing ADCC in vitro. Our antibody also effectively binds and stabilizes MICA/B expression in additional tumor types and demonstrates broad specificity. We show that in two KL mutant NSCLC xenograft models and a KL mutant PDX model, treatment with AHA-1031 monotherapy significantly inhibits tumor growth compared with vehicle-treated animals with no observable toxicity. Tumor tissues from treated mice exhibit significantly increased immune cell infiltrates and activated NK cell populations.
conclusionsActivating NK cells through MICA/B stabilization and inducing ADCC offers an alternative and potent therapy option in KL tumors. MICA/B are shed across different tumors making this therapeutic strategy universally applicable.
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Registered trials
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 Socratic graph.