Anti-CD44 Variant 10 Monoclonal Antibody Exerts Antitumor Activity in Mouse Xenograft Models of Oral Squamous Cell Carcinomas DOI Open Access

Kenichiro Ishikawa,

Hiroyuki Suzuki, Tomokazu Ohishi

et al.

Published: Aug. 6, 2024

CD44 regulates cell adhesion, proliferation, survival, and stemness has been considered a tumor therapy target. possesses the shortest standard (CD44s) variety of variant (CD44v) isoforms. Since expression CD44v is restricted in epithelial cells carcinomas compared to CD44s, promising target for monoclonal antibody (mAb) therapy. We previously developed an anti‐CD44v10 mAb, C44Mab-18 (IgM, kappa) recognize exon 10-encoded region. In present study, mouse IgG2a version (C44Mab-18-mG2a) was generated evaluate antitumor activities against CD44-positive with established anti-pan C44Mab-46-mG2a. C44Mab-18-mG2a exhibited higher reactivity C44Mab-46-mG2a CD44v3–10-overexpressed CHO-K1 (CHO/CD44v3–10) oral squamous carcinoma lines (HSC-2 SAS) flow cytometry. exerted superior antibody‐dependent cellular cytotoxicity (ADCC) CD44v3–10. contrast, showed complement‐dependent (CDC) A similar tendency observed ADCC CDC HSC-2 SAS. Furthermore, administering or significantly suppressed CD44v3–10, HSC-2, SAS xenograft growth control IgG2a. These results indicate that could be therapeutic regimen CD44v10-positive tumors.

Language: Английский

Antitumor activities of anti‑CD44 monoclonal antibodies in mouse xenograft models of esophageal cancer DOI Creative Commons

Kenichiro Ishikawa,

Hiroyuki Suzuki, Tomokazu Ohishi

et al.

Oncology Reports, Journal Year: 2024, Volume and Issue: 52(5)

Published: Aug. 29, 2024

CD44 is a type I transmembrane glycoprotein associated with poor prognosis in various solid tumors. Since plays critical role tumor development by regulating cell adhesion, survival, proliferation and stemness, it has been considered target for therapy. Anti‑CD44 monoclonal antibodies (mAbs) have developed applied to antibody‑drug conjugates chimeric antigen receptor‑T Anti-pan‑CD44 mAbs, C44Mab‑5 C44Mab‑46, which recognize both standard (CD44s) variant isoforms were previously developed. The present study generated mouse IgG2a version of the anti‑pan‑CD44 mAbs (5‑mG2a C44Mab‑46‑mG2a) evaluate antitumor activities against CD44‑positive cells. Both 5‑mG2a C44Mab‑46‑mG2a recognized CD44s‑overexpressed CHO‑K1 (CHO/CD44s) cells esophageal line (KYSE770) flow cytometry. Furthermore, could activate effector presence CHO/CD44s exhibited complement-dependent cytotoxicity KYSE770 administration significantly suppressed xenograft compared control IgG2a. These results indicate that exert cancers be promising therapeutic regimen

Language: Английский

Citations

7
Epitope Mapping of an Anti-Mouse CD39 Monoclonal Antibody Using PA Scanning and RIEDL Scanning DOI
Yuki Okada, Hiroyuki Suzuki, Tomohiro Tanaka

et al.

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Journal Year: 2024, Volume and Issue: 43(2), P. 44 - 52

Published: March 20, 2024

A cell-surface ectonucleotidase CD39 mediates the conversion of extracellular adenosine triphosphate into immunosuppressive with another CD73. The elevated in tumor microenvironment attenuates antitumor immunity, which promotes cell immunologic escape and progression. Anti-CD39 monoclonal antibodies (mAbs), suppress enzymatic activity, can be applied to therapy. Therefore, an understanding relationship between inhibitory activity epitope mAbs is important. We previously established anti-mouse (anti-mCD39) mAb, C

Language: Английский

Citations

4
Anti-CD44 Variant 10 Monoclonal Antibody Exerts Antitumor Activity in Mouse Xenograft Models of Oral Squamous Cell Carcinomas DOI Open Access

Kenichiro Ishikawa,

Hiroyuki Suzuki, Tomokazu Ohishi

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9190 - 9190

Published: Aug. 24, 2024

CD44 regulates cell adhesion, proliferation, survival, and stemness has been considered a tumor therapy target. possesses the shortest standard (CD44s) variety of variant (CD44v) isoforms. Since expression CD44v is restricted in epithelial cells carcinomas compared to CD44s, promising target for monoclonal antibody (mAb) therapy. We previously developed an anti-CD44v10 mAb, C

Language: Английский

Citations

3
Establishment of a Novel Anti-CD44 Variant 10 Monoclonal Antibody C44Mab-18 for Immunohistochemical Analysis against Oral Squamous Cell Carcinomas DOI Creative Commons

Kenichiro Ishikawa,

Hiroyuki Suzuki, Mika K. Kaneko

et al.

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(7), P. 5248 - 5262

Published: June 21, 2023

Head and neck squamous cell carcinoma (HNSCC) is the most common type of head cancer, has been revealed as second-highest expression CD44 in cancers. investigated a cancer stem marker HNSCC plays critical role tumor malignant progression. Especially, splicing variant isoforms (CD44v) are overexpressed cancers considered promising target for diagnosis therapy. We developed monoclonal antibodies (mAbs) against by immunizing mice with CD44v3–10-overexpressed PANC-1 cells. Among established clones, C44Mab-18 (IgM, kappa) reacted CHO/CD44v3–10, but not CHO/CD44s parental CHO-K1 using flow cytometry. The epitope mapping peptides that cover exon-encoded regions recognized border sequence between 10 constant exon 16-encoded sequence. These results suggest recognizes 10-containing CD44v, CD44s. Furthermore, could recognize human oral (OSCC) line, HSC-3, apparent dissociation (KD) CHO/CD44v3–10 HSC-3 was 1.6 × 10−7 M 1.7 M, respectively. detected CD44v3–10 Western blotting, endogenous CD44v10 immunohistochemistry OSCC tissues. indicate useful detecting cytometry immunohistochemistry.

Language: Английский

Citations

8
EMab-300 Detects Mouse Epidermal Growth Factor Receptor-Expressing Cancer Cell Lines in Flow Cytometry DOI Creative Commons

Nohara Goto,

Hiroyuki Suzuki, Tomohiro Tanaka

et al.

Antibodies, Journal Year: 2023, Volume and Issue: 12(3), P. 42 - 42

Published: June 21, 2023

Epidermal Growth Factor Receptor (EGFR) overexpression or its mutation mediates the sustaining proliferative signaling, which is an important hallmark of cancer. Human EGFR-targeting monoclonal antibody (mAb) therapy such as cetuximab has been approved for clinical use in patients with colorectal cancers and head neck squamous cell carcinomas. A reliable preclinical mouse model essential to further develop mAb against EGFR. Therefore, sensitive mAbs EGFR (mEGFR) should be established. In this study, we developed a specific mEGFR using Cell-Based Immunization Screening (CBIS) method. The established anti-mEGFR mAb, EMab-300 (rat IgG1, kappa), reacted mEGFR-overexpressed Chinese hamster ovary-K1 (CHO/mEGFR) endogenously mEGFR-expressed lines, including NMuMG (a mammary gland epithelial cell) Lewis lung carcinoma cells, flow cytometry. kinetic analysis cytometry indicated that KD CHO/mEGFR was 4.3 × 10-8 M 1.9 M, respectively. These results applies detection may useful obtain proof concept studies.

Language: Английский

Citations

8
Development of a Novel Anti-CD44 Variant 8 Monoclonal Antibody C44Mab-94 against Gastric Carcinomas DOI Creative Commons
Hiroyuki Suzuki,

Nohara Goto,

Tomohiro Tanaka

et al.

Antibodies, Journal Year: 2023, Volume and Issue: 12(3), P. 45 - 45

Published: July 4, 2023

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. GC with peritoneal metastasis exhibits a poor prognosis due to lack effective therapy. A comprehensive analysis malignant ascites identified genomic alterations and significant amplifications driver genes, including CD44. CD44 its splicing variants are overexpressed in tumors, play crucial roles acquisition invasiveness, stemness, resistance treatments. Therefore, development CD44-targeted monoclonal antibodies (mAbs) important for diagnosis In this study, we immunized mice CD44v3-10-overexpressed PANC-1 cells established several dozens clones that produce anti-CD44v3-10 mAbs. One (C44Mab-94; IgG1, kappa) recognized variant-8-encoded region peptide, indicating C44Mab-94 specific mAb CD44v8. Furthermore, could recognize CHO/CD44v3-10 cells, oral squamous cell carcinoma line (HSC-3), or lines (MKN45 NUGC-4) flow cytometric analyses. detect exogenous CD44v3-10 endogenous CD44v8 western blotting stained formalin-fixed paraffin-embedded gastric cells. These results indicate useful detecting variety experimental methods expected become usefully applied

Language: Английский

Citations

4
Potential Immunohistochemical Biomarkers for Grading Oral Dysplasia: A Literature Review DOI Creative Commons
Jakub Zdrojewski, Monika Nowak, Kacper Nijakowski

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 577 - 577

Published: March 5, 2024

Oral cancer is a prevalent global health issue, with significant morbidity and mortality rates. Despite available preventive measures, it remains one of the most common cancers, emphasising need for improved diagnostic prognostic tools. This review focuses on oral potentially malignant disorders (OPMDs), precursors to cancer, specifically epithelial dysplasia (OED). The World Health Organisation (WHO) provides three-tier grading system OED, recent updates have expanded criteria enhance precision. In evaluation histological presently regarded as gold standard; however, its subjectivity unreliability in anticipating transformation or recurrence pose notable limitations. primary objective investigate whether specific immunohistochemical biomarkers can OED assessment according WHO classification. Biomarkers exhibit potential comprehensive risk evaluation, early detection, diagnosis, prognosis, treatment optimisation. Technological advancements, including sequencing nanotechnology, detection capabilities. Some analysed are frequently chosen, such p53, Ki-67, cadherins/catenins, other proteins used differentiate grades. However, further research needed confirm these findings discover new precise minimally invasive transformation.

Language: Английский

Citations

1
Beta cells deficient for Renalase counteract autoimmunity by shaping natural killer cell activity DOI Creative Commons
Kevin Bode, Siying Wei, I. M. Gruber

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 4, 2024

Type 1 diabetes (T1D) arises from autoimmune-mediated destruction of insulin-producing pancreatic beta cells. Recent advancements in the technology generating cells human pluripotent stem (SC-beta cells) have facilitated exploration cell replacement therapies for treating T1D. However, persistent threat autoimmunity poses a significant challenge to survival transplanted SC-beta Genetic engineering is promising approach enhance immune resistance as we previously showed by inactivating Renalase (Rnls) gene. Here, demonstrate that Rnls loss function shapes mediating regulatory natural killer (NK) phenotype important induction tolerogenic antigen-presenting Rnls-deficient mediate cell-cell contact-independent hallmark anti-inflammatory cytokine Tgfβ1 NK In addition, surface expression checkpoints CD47 and Ceacam1 markedly elevated on deficient Rnls. Altered glucose metabolism mutant involved upregulation expression. These findings are crucial better understand how genetically engineered shape autoimmunity, giving valuable insights future therapeutic treat cure

Language: Английский

Citations

1
Promotion of squamous cell carcinoma tumorigenesis by oncogene‐mediated THG‐1/TSC22D4 phosphorylation DOI Creative Commons

Nohara Goto,

Hiroyuki Suzuki, Ling Zheng

et al.

Cancer Science, Journal Year: 2023, Volume and Issue: 114(10), P. 3972 - 3983

Published: Aug. 22, 2023

Carcinoma cells possess high proliferative and invasive potentials exhibit a resilience against stresses, metabolic disorder, therapeutic efforts. These properties are mainly acquired by genetic alterations including driver gene mutations. However, the detailed molecular mechanisms have not been fully elucidated. Here, we provide novel mechanism connecting oncogenic signaling tumorigenic transforming growth factor-β1-stimulated clone 22 (TSC-22) family protein, THG-1 (also called as TSC22D4). is localized at basal layer of normal squamous epithelium overexpressed in cell carcinomas (SCCs). knockdown suppressed SCC proliferation, invasiveness, xenograft tumor formation. In contrast, overexpression promoted EGF-induced proliferation stratified Furthermore, phosphorylated receptor tyrosine kinase (RTK)-RAS-ERK pathway, which oncogene-mediated tumorigenesis. Moreover, involves alternative splicing CD44 variants, regulator stemness, oxidative stress resistance under RTK pathway. findings highlight pivotal roles effector tumorigenesis, detection phosphorylation our established specific antibody could contribute to cancer diagnosis therapy.

Language: Английский

Citations

3
EMab-300 Detects Mouse Epidermal Growth Factor Receptor-Expressing Cancer Cell Lines in Flow Cytometry DOI Open Access

Nohara Goto,

Hiroyuki Suzuki, Tomohiro Tanaka

et al.

Published: May 9, 2023

The Epidermal Growth Factor Receptor (EGFR) overexpression or its mutation mediates the sustaining proliferative signaling in cancers. Human EGFR-targeting monoclonal antibody (mAb) therapy such as cetuximab has been approved for clinical use patients with colorectal cancers and head neck squamous cell carcinomas. A reliable preclinical mouse model is essential to further develop mAb against EGFR. However, a EGFR (mEGFR) flow cytometry not established. In this study, we developed specific sensitive mEGFR using Cell-Based Immunization Screening (CBIS) method. established anti-mEGFR mAb, EMab-300 (rat IgG1, kappa) reacted mEGFR-overexpressed Chinese hamster ovary-K1 (CHO/mEGFR) endogenously mEGFR-expressed lines, including NMuMG (a mammary gland epithelial cell) Lewis lung carcinoma cells by cytometry. kinetic analysis indicated that dissociation constant (KD) of CHO/mEGFR was 4.3 × 10−8 M 1.9 M, respectively. These results applies detection cytometry, expected study.

Language: Английский

Citations

2