ArticleInternational journal of cancer2013
Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors.
Article in International journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 76 citations in OpenAlex.
- Research progress on platelets in glioma.Chinese medical journal · 2025Review
- Medulloblastoma: biology and immunotherapy.Frontiers in immunology · 2025Review
- A Synopsis of Biomarkers in Glioblastoma: Past and Present.Current issues in molecular biology · 2024Review
- Exosome-transmitted podoplanin promotes tumor-associated macrophage-mediated immune tolerance in glioblastoma.CNS neuroscience & therapeutics · 2024Article
- Development of a Novel Anti-CD44 Variant 4 Monoclonal Antibody CCurrent issues in molecular biology · 2023Article
- Efficacy of cancer-specific anti-podoplanin CAR-T cells and oncolytic herpes virus G47Δ combination therapy against glioblastoma.Molecular therapy oncolytics · 2022Article
- Review
- Podoplanin: Its roles and functions in neurological diseases and brain cancers.Frontiers in pharmacology · 2022Review
- Tumor Cell-Induced Platelet Aggregation as an Emerging Therapeutic Target for Cancer Therapy.Frontiers in oncology · 2022Review
- The Role of Podoplanin in the Immune System and Inflammation.Journal of inflammation research · 2022Review
- Review
- A Modified Nucleoside 6-Thio-2'-Deoxyguanosine Exhibits Antitumor Activity in Gliomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Article
- Inflammatory cell-associated tumors. Not only macrophages (TAMs), fibroblasts (TAFs) and neutrophils (TANs) can infiltrate the tumor microenvironment. The unique role of tumor associated platelets (TAPs).Cancer immunology, immunotherapy : CII · 2021Review
- Tumor-infiltrating podoplaninOncoimmunology · 2020Article
- Therapeutic efficacy evaluation of radioimmunotherapy withCancer science · 2019Article
- Intratumoral platelet aggregate formation in a murine preclinical glioma model depends on podoplanin expression on tumor cells.Blood advances · 2019Article
- Sym004-induced EGFR elimination is associated with profound anti-tumor activity in EGFRvIII patient-derived glioblastoma models.Journal of neuro-oncology · 2018Article
- Podoplanin: An emerging cancer biomarker and therapeutic target.Cancer science · 2018Review
- Plasma soluble podoplanin is a novel marker for the diagnosis of tumor occurrence and metastasis.Cancer science · 2018Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Our study demonstrates the glioma tumor antigen podoplanin to be present at very high levels (>90%) in both glioblastoma (D2159MG, D08-0308MG and D08-0493MG) and medulloblastoma (D283MED, D425MED and DAOY) xenografts and cell line. We constructed a novel recombinant single-chain antibody variable region fragment (scFv), NZ-1, specific for podoplanin from the NZ-1 hybridoma. NZ-1-scFv was then fused to Pseudomonas exotoxin A, carrying a C-terminal KDEL peptide (NZ-1-PE38KDEL). The immunotoxin (IT) was further stabilized by a disulfide (ds) bond between the heavy-chain and light-chain variable regions as the construct NZ-1-(scdsFv)-PE38KDEL. NZ-1-(scdsFv)-PE38KDEL exhibited significant reactivity to glioblastoma and medulloblastoma cells. The affinity of NZ-1-(scdsFv), NZ-1-(scdsFv)-PE38KDEL and NZ-1 antibody for podoplanin peptide was 2.1 × 10(-8) M, 8.0 × 10(-8) M and 3.9 × 10(-10) M, respectively. In a protein stability assay, NZ-1-(scdsFv)-PE38KDEL retained 33-98% of its activity, whereas that of NZ-1-PE38KDEL declined to 13% of its initial levels after incubation at 37°C for 3 days. In vitro cytotoxicity of the NZ-1-(scdsFv)-PE38KDEL was measured in cells isolated from glioblastoma xenografts, D2159MG, D08-0308MG and D08-0493MG, and in the medulloblastoma D283MED, D425MED and DOAY xenografts and cell line. The NZ-1-(scdsFv)-PE38KDEL IT was highly cytotoxic, with an 50% inhibitory concentration in the range of 1.6-29 ng/ml. Significantly, NZ-1-(scdsFv)-PE38KDEL demonstrated tumor growth delay, averaging 24 days (p < 0.001) and 21 days (p < 0.001) in D2159MG and D283MED in vivo tumor models, respectively. Crucially, in the D425MED intracranial tumor model, NZ-1-(scdsFv)-PE38KDEL caused a 41% increase in survival (p ≤ 0.001). In preclinical studies, NZ-1-(scdsFv)-PE38KDEL exhibited significant potential as a targeting agent for malignant brain tumors.
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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.