ArticleJournal of hematology & oncology2014
A novel mycobacterial Hsp70-containing fusion protein targeting mesothelin augments antitumor immunity and prolongs survival in murine models of ovarian cancer and mesothelioma.
Article in Journal of hematology & oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- The Conjugation of Antibodies to Heat Shock Protein 70 Activates Immune Responses Against Tumor Cells.ImmunoTargets and therapy · 2026Article
- Combining Chemotherapeutic Agents, Targeted Therapies, Vaccines and Natural Bioactive Compounds for Mesothelioma: Advances and Perspectives.Oncology research · 2025Review
- Efficacy and safety of novel multiple-chain DAP-CAR-T cells targeting mesothelin in ovarian cancer and mesothelioma: a single-arm, open-label and first-in-human study.Genome medicine · 2024Article
- Article
- Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target.Frontiers in oncology · 2024Review
- Identification of Tumor Antigens and Immune Subtypes of Malignant Mesothelioma for mRNA Vaccine Development.Vaccines · 2022Article
- A Novel PD-L1-Containing MSLN Targeting Vaccine for Lung Cancer Immunotherapy.Frontiers in immunology · 2022Article
- Hitting the Bull's-Eye: Mesothelin's Role as a Biomarker and Therapeutic Target for Malignant Pleural Mesothelioma.Cancers · 2021Review
- Systemic characterization of alternative splicing related to prognosis and immune infiltration in malignant mesothelioma.BMC cancer · 2021Article
- Remission-Stage Ovarian Cancer Cell Vaccine with Cowpea Mosaic Virus Adjuvant Prevents Tumor Growth.Cancers · 2021Article
- Review
- CD90Oncotarget · 2019Article
- Methods for improving the immunogenicity and efficacy of cancer vaccines.Expert opinion on biological therapy · 2018Review
- Human DKK1 and human HSP70 fusion DNA vaccine induces an effective anti-tumor efficacy in murine multiple myeloma.Oncotarget · 2018Article
- Peripheral T-Cell Reactivity to Heat Shock Protein 70 and Its Cofactor GrpE from Tropheryma whipplei Is Reduced in Patients with Classical Whipple's Disease.Infection and immunity · 2017Article
- Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells.Journal of hematology & oncology · 2017Article
- HSP70-based anti-cancer immunotherapy.Human vaccines & immunotherapeutics · 2016Article
- Cancer Vaccines in Ovarian Cancer: How Can We Improve?Biomedicines · 2016Review
- Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies.Expert review of respiratory medicine · 2015Review
- Antimelanoma CTL recognizes peptides derived from an ORF transcribed from the antisense strand of the 3' untranslated region of TRIT1.Molecular therapy oncolytics · 2015Article
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Authors and funding
23 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough dendritic cell (DC) vaccines are considered to be promising treatments for advanced cancer, their production and administration is costly and labor-intensive. We developed a novel immunotherapeutic agent that links a single-chain antibody variable fragment (scFv) targeting mesothelin (MSLN), which is overexpressed on ovarian cancer and mesothelioma cells, to Mycobacterium tuberculosis (MTB) heat shock protein 70 (Hsp70), which is a potent immune activator that stimulates monocytes and DCs, enhances DC aggregation and maturation and improves cross-priming of T cells mediated by DCs.
methodsBinding of this fusion protein with MSLN on the surface of tumor cells was measured by flow cytometry and fluorescence microscopy. The therapeutic efficacy of this fusion protein was evaluated in syngeneic and orthotopic mouse models of papillary ovarian cancer and malignant mesothelioma. Mice received 4 intraperitoneal (i.p.) treatments with experimental or control proteins post i.p. injection of tumor cells. Ascites-free and overall survival time was measured. For the investigation of anti-tumor T-cell responses, a time-matched study was performed. Splenocytes were stimulated with peptides, and IFNγ- or Granzyme B- generating CD3+CD8+ T cells were detected by flow cytometry. To examine the role of CD8+ T cells in the antitumor effect, we performed in vivo CD8+ cell depletion. We further determined if the fusion protein increases DC maturation and improves antigen presentation as well as cross-presentation by DCs.
resultsWe demonstrated in vitro that the scFvMTBHsp70 fusion protein bound to the tumor cells used in this study through the interaction of scFv with MSLN on the surface of these cells, and induced maturation of bone marrow-derived DCs. Use of this bifunctional fusion protein in both mouse models significantly enhanced survival and slowed tumor growth while augmenting tumor-specific CD8+ T-cell dependent immune responses. We also demonstrated in vitro and in vivo that the fusion protein enhanced antigen presentation and cross-presentation by targeting tumor antigens towards DCs.
conclusionsThis new cancer immunotherapy has the potential to be cost-effective and broadly applicable to tumors that overexpress mesothelin.
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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.