ArticleMolecular oncology2016
Characterization of a re-engineered, mesothelin-targeted Pseudomonas exotoxin fusion protein for lung cancer therapy.
Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 56 citations in OpenAlex.
- Phase I/II Study of the Mesothelin-targeted Immunotoxin LMB-100 with Nab-Paclitaxel for Patients with Advanced Pancreatic Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Mesothelin biology and the evolving landscape of targeted immunotherapy.Molecular therapy. Oncology · 2026Review
- Taming Bacterial Toxins into an Anticancer Platform.Biochemical and biophysical research communications · 2025Article
- Decoding the role of mesothelin in tumor dynamics and targeted treatment innovations.Molecular biomedicine · 2025Review
- Review
- Potentiating intratumoral therapy with immune checkpoint inhibitors: shifting the paradigm of multimodality therapeutics.Immuno-oncology technology · 2025Review
- Article
- Current Status and Future Perspectives of Antibody-Drug Conjugates in Hormone Receptor-Positive Breast Cancer.Cancers · 2024Review
- Cadherin 17 Nanobody-Mediated Near-Infrared-II Fluorescence Imaging-Guided Surgery and Immunotoxin Delivery for Colorectal Cancer.Biomaterials research · 2024Article
- Challenges of Anti-Mesothelin CAR-T-Cell Therapy.Cancers · 2023Review
- Systemic immune changes accompany combination treatment with immunotoxin LMB-100 and nab-paclitaxel.Cancer medicine · 2023Article
- Antibody-drug conjugates in lung cancer: dawn of a new era?NPJ precision oncology · 2023Review
- The past, present, and future of targeted therapeutic approaches in patients with diffuse pleural mesotheliomas.Journal of cancer metastasis and treatment · 2023Article
- Anti-mesothelin immunotoxin induces mesothelioma eradication, anti-tumor immunity, and the development of tertiary lymphoid structures.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Chimeric antigen receptor T cells engineered to recognize the P329G-mutated Fc part of effector-silenced tumor antigen-targeting human IgG1 antibodies enable modular targeting of solid tumors.Journal for immunotherapy of cancer · 2022Article
- Advances on Delivery of Cytotoxic Enzymes as Anticancer Agents.Molecules (Basel, Switzerland) · 2022Review
- Development and Evaluation of Competitive Inhibitors of Trastuzumab-HER2 Binding to Bypass the Binding-Site Barrier.Frontiers in pharmacology · 2022Article
- Engineered antibody fusion proteins for targeted disease therapy.Trends in pharmacological sciences · 2021Review
- Phase 2 Study of Olaparib in Malignant Mesothelioma and Correlation of Efficacy With Germline or Somatic Mutations inJTO clinical and research reports · 2021Article
- Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,679 Tumors.Biomedicines · 2021Article
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
Abstract
Mesothelin overexpression in lung adenocarcinomas correlates with the presence of activating KRAS mutations and poor prognosis. Hence SS1P, a mesothelin-targeted immunotoxin, could offer valuable treatment options for these patients, but its use in solid tumor therapy is hampered by high immunogenicity and non-specific toxicity. To overcome both obstacles we developed RG7787, a de-immunized cytotoxic fusion protein comprising a humanized SS1 Fab fragment and a truncated, B-cell epitope silenced, 24 kD fragment of Pseudomonas exotoxin A (PE24). Reactivity of RG7787 with sera from immunotoxin-treated patients was >1000 fold reduced. In vitro RG7787 inhibited cell viability of lung cancer cell lines with picomolar potency. The pharmacokinetic properties of RG7787 in rodents were comparable to SS1P, yet it was tolerated up to 10 fold better without causing severe vascular leak syndrome or hepatotoxicity. A pharmacokinetic/pharmacodynamic model developed based on NCI-H596 xenograft studies showed that for RG7787 and SS1P, their in vitro and in vivo potencies closely correlate. At optimal doses of 2-3 mg/kg RG7787 is more efficacious than SS1P. Even large, well established tumors (600 mm(3)) underwent remission during three treatment cycles with RG7787. Also in two patient-derived lung cancer xenograft models, Lu7336 and Lu7187, RG7787 showed anti-tumor efficacy. In monotherapy two treatment cycles were moderately efficacious in the Lu7336 model but showed good anti-tumor activity in the KRAS mutant Lu7187 model (26% and 80% tumor growth inhibition, respectively). Combination of RG7787 with standard chemotherapies further enhanced efficacy in both models achieving near complete eradication of Lu7187 tumors.
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