ArticleJournal for immunotherapy of cancer2020
PODO447: a novel antibody to a tumor-restricted epitope on the cancer antigen podocalyxin.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- A Cancer-Specific Anti-Podocalyxin Monoclonal Antibody (humPcMab-60) Demonstrated Antitumor Efficacy in Pancreatic and Colorectal Cancer Xenograft Models.Antibodies (Basel, Switzerland) · 2025Article
- Article
- A Cancer-Specific Monoclonal Antibody against Podocalyxin Exerted Antitumor Activities in Pancreatic Cancer Xenografts.International journal of molecular sciences · 2023Article
- Inaugurating High-Throughput Profiling of Extracellular Vesicles for Earlier Ovarian Cancer Detection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function.Science advances · 2023Article
- VT68.2: An Antibody to Chondroitin Sulfate Proteoglycan 4 (CSPG4) Displays Reactivity against a Tumor-Associated Carbohydrate Antigen.International journal of molecular sciences · 2023Article
- A tumor-restricted glycoform of podocalyxin is a highly selective marker of immunologically cold high-grade serous ovarian carcinoma.Frontiers in oncology · 2023Article
- Measuring the multifaceted roles of mucin-domain glycoproteins in cancer.Advances in cancer research · 2023Review
- Identification of ARAP3 as a regulator of tumor progression, macrophage infiltration and osteoclast differentiation in a tumor microenvironment-related prognostic model of Ewing sarcoma.American journal of cancer research · 2023Article
- High expression of theAnnals of translational medicine · 2022Article
- Revealing the human mucinome.Nature communications · 2022Article
- Review
- Targeting a Tumor-Specific Epitope on Podocalyxin Increases Survival in Human Tumor Preclinical Models.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe success of new targeted cancer therapies has been dependent on the identification of tumor-specific antigens. Podocalyxin (Podxl) is upregulated on tumors with high metastatic index and its presence is associated with poor outcome, thus emerging as an important prognostic and theragnostic marker in several human cancers. Moreover, in human tumor xenograft models, Podxl expression promotes tumor growth and metastasis. Although a promising target for immunotherapy, the expression of Podxl on normal vascular endothelia and kidney podocytes could hamper efforts to therapeutically target this molecule. Since pathways regulating post-translational modifications are frequently perturbed in cancer cells, we sought to produce novel anti-Podxl antibodies (Abs) that selectively recognize tumor-restricted glycoepitopes on the extracellular mucin domain of Podxl.
methodsSplenic B cells were isolated from rabbits immunized with a Podxl-expressing human tumor cell line. Abs from these B cells were screened for potent reactivity to Podxl
resultsOne mAb (PODO447) showed strong reactivity with a variety of Podxl+ tumor cell lines but not with normal primary human tissue including Podxl+ kidney podocytes and most vascular endothelia. Screening of an ovarian carcinoma TMA (219 cases) revealed PODO447 reactivity with the majority of tumors, including 65% of the high-grade serous histotype. Subsequent biochemical analyses determined that PODO447 reacts with a highly unusual terminal N-acetylgalactosamine beta-1 (GalNAcβ1) motif predominantly found on the Podxl protein core. Finally, Ab-drug conjugates showed specific efficacy in killing tumor cells
conclusionsWe have generated a novel and exquisitely tumor-restricted mAb, PODO447, that recognizes a glycoepitope on Podxl expressed at high levels by a variety of tumors including the majority of life-threatening high-grade serous ovarian tumors. Thus, tumor-restricted PODO447 exhibits the appropriate specificity for further development as a targeted immunotherapy.
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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.