ArticleCancer cell international2023
ITC-6102RO, a novel B7-H3 antibody-drug conjugate, exhibits potent therapeutic effects against B7-H3 expressing solid tumors.
Article in Cancer cell international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 19 citations in OpenAlex.
- Enabling the synthesis of multi-payload thio-antibody conjugates through the use of pyridazinediones,RSC chemical biology · 2026Article
- Updates on Antibody Drug Conjugates and Bispecific T-Cell Engagers in SCLC.Antibodies (Basel, Switzerland) · 2026Review
- Clinical applications of antibody-drug conjugates in advanced non-small cell lung cancer.Frontiers in immunology · 2026Review
- The B7-H3 (CD276) pathway: emerging biology and clinical therapeutics.Trends in pharmacological sciences · 2025Review
- Setdb1 ablation in macrophages attenuates fibrosis in heart allografts.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- B7-H3-liquid biopsy for the characterization and monitoring of the dynamic biology of prostate cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2025Article
- Immunological mechanisms and antibody-drug conjugates targeting B7-H3 and B7-H4 in ovarian cancer.Frontiers in immunology · 2025Review
- B7-H3/CD276: Novel Immune Checkpoint and Jack of All Trades.ImmunoTargets and therapy · 2025Review
- Antibody-drug conjugates in cancer therapy: current advances and prospects for breakthroughs.Frontiers in cell and developmental biology · 2025Review
- Histone lactylation-driven B7-H3 expression promotes tumor immune evasion.Theranostics · 2025Article
- Radiomic features based on pyradiomics predict CD276 expression associated with breast cancer prognosis.Heliyon · 2024Article
- Research progress on novel antibody drug conjugates in cancer therapy.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Review
- B7-H3 in glioblastoma and beyond: significance and therapeutic strategies.Frontiers in immunology · 2024Review
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe B7-H3 protein, encoded by the CD276 gene, is a member of the B7 family of proteins and a transmembrane glycoprotein. It is highly expressed in various solid tumors, such as lung and breast cancer, and has been associated with limited expression in normal tissues and poor clinical outcomes across different malignancies. Additionally, B7-H3 plays a crucial role in anticancer immune responses. Antibody-drug conjugates (ADCs) are a promising therapeutic modality, utilizing antibodies targeting tumor antigens to selectively and effectively deliver potent cytotoxic agents to tumors.
methodsIn this study, we demonstrate the potential of a novel B7-H3-targeting ADC, ITC-6102RO, for B7-H3-targeted therapy. ITC-6102RO was developed and conjugated with dHBD, a soluble derivative of pyrrolobenzodiazepine (PBD), using Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linkers with high biostability. We assessed the cytotoxicity and internalization of ITC-6102RO in B7-H3 overexpressing cell lines in vitro and evaluated its anticancer efficacy and mode of action in B7-H3 overexpressing cell-derived and patient-derived xenograft models in vivo.
resultsITC-6102RO inhibited cell viability in B7-H3-positive lung and breast cancer cell lines, inducing cell cycle arrest in the S phase, DNA damage, and apoptosis in vitro. The binding activity and selectivity of ITC-6102RO with B7-H3 were comparable to those of the unconjugated anti-B7-H3 antibody. Furthermore, ITC-6102RO proved effective in B7-H3-positive JIMT-1 subcutaneously xenografted mice and exhibited a potent antitumor effect on B7-H3-positive lung cancer patient-derived xenograft (PDX) models. The mode of action, including S phase arrest and DNA damage induced by dHBD, was confirmed in JIMT-1 tumor tissues.
conclusionsOur preclinical data indicate that ITC-6102RO is a promising therapeutic agent for B7-H3-targeted therapy. Moreover, we anticipate that OHPAS linkers will serve as a valuable platform for developing novel ADCs targeting a wide range of targets.
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