A Cancer-Specific Monoclonal Antibody against HER2 Exerts Antitumor Activities in Human Breast Cancer Xenograft Models

Kaneko, Mika K.; Suzuki, Hiroyuki; Ohishi, Tomokazu; Nakamura, Takuro; Tanaka, Tomohiro; Kato, Yukinari

doi:10.3390/ijms25031941

Cited by 9 publications

(2 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have developed cancer-specific mAbs (CasMabs) against HER2 (H2Mab-214 [44] and H2Mab-250 [45]), podocalyxin (PcMab-6 [46] and PcMab-60 [47]), and podoplanin (LpMab-2 [48] and LpMab-23 [49]) and evaluated the reactivity to cancer and normal cells in flow cytometry. We also reported the antitumor effect in mouse xenograft models using the defucosylated mouse IgG2a or human IgG1 types recombinant mAbs [44,46,[48][49][50][51][52]. Some anti-CD44 mAbs which exhibit cancer specificity have been reported [53].…”

Section: Discussionmentioning

confidence: 94%

Defucosylated Anti-CD44 Monoclonal Antibodies Exert Antitumor Activities against Esophageal Tumor Xenograft

Ishikawa,

Suzuki,

Ohishi

et al. 2024

Preprint

View full text Add to dashboard Cite

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

show abstract

Section: Discussionmentioning

confidence: 94%

Defucosylated Anti-CD44 Monoclonal Antibodies Exert Antitumor Activities against Esophageal Tumor Xenograft

Ishikawa,

Suzuki,

Ohishi

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…[45] Furthermore, some of the developed mAbs by the CBIS method exhibited cancer specificity by recognizing unique cancer-specific epitopes. [46][47][48][49][50][51] Therefore, the CBIS method is an efficient and useful tactic for generating diverse antibodies targeting membrane proteins.…”

Section: Discussionmentioning

confidence: 99%

C<sub>8</sub>Mab-21: A Novel Anti-human CCR8 Monoclonal Antibody for Flow Cytometry

Tanaka,

Suzuki,

et al. 2024

Preprint

View full text Add to dashboard Cite

C-C motif chemokine receptor-8 (CCR8) belongs to class A of G protein-coupled receptors (GPCRs). CCR8 interacts with the specific chemokine ligand CCL1/I-309 in humans, which is produced by various cells, including tumor-associated macrophages and regulatory T cells (Treg). CCR8 is highly expressed on Treg and T-helper 2 (TH2) cells recruited to the inflammation site and is implicated in allergy, asthma, and cancer progression. The CCR8+Treg has been suggested to be an important regulator in the immunosuppressive tumor microenvironment (TME); therefore, it has been desired to develop sensitive monoclonal antibodies (mAbs) for CCR8. This study developed a specific mAb for human CCR8 (hCCR8), which is useful for flow cytometry by employing the Cell-Based Immunization and Screening (CBIS) method. The established anti-hCCR8 mAb, C8Mab-21, (mouse IgM, kappa) reacted with hCCR8-overexpressed Chinese hamster ovary-K1 (CHO/hCCR8) cells, TALL-1 (acute T lymphoblastic leukemia), CCRF-HSB2 (human T-lymphoblastic leukemia), and natural killer cells, which express endogenous hCCR8 by flow cytometry. Furthermore, C8Mab-21 demonstrated a moderate binding affinity for CHO/hCCR8 and TALL-1 with a dissociation constant of 6.5×10-8 M and 2.0×10-8 M, respectively. C8Mab-21, which was established by the CBIS method, could be a useful tool for analyzing the hCCR8-related biological response using flow cytometry.

show abstract

Nimotuzumab and irinotecan synergistically induce ROS‐mediated apoptosis by endoplasmic reticulum stress and mitochondrial‐mediated pathway in cervical cancer

Teng,

Zhao

2024

Biotech and App Biochem

View full text Add to dashboard Cite

Irinotecan (CPT‐11), a chemotherapeutic agent used to treat several types of cancer, induces cytotoxic effects on healthy cells. The epidermal growth factor receptor (EGFR) plays a crucial role in various forms of cancer. Nimotuzumab (NmAb), a monoclonal antibody that targets the EGFR, is utilized in some countries to treat malignancies that have an overexpression of EGFR. Yet, there is a lack of literature on the potential anticancer properties of the CPT‐11 and NmAb combination on in vitro human cervical cancer cells. This study investigates the apoptosis mode of the CPT‐11 and NmAb combination on cervical HeLa cancer cells. The Annexin V/propidium iodide staining examination demonstrated that the combination of CPT‐11 and NmAb resulted in a decrease in the number of viable cells and more potent induction of cell apoptosis than the effects of CPT‐11 or NmAb alone in HeLa cells. Furthermore, the combined treatment resulted in elevated levels of reactive oxygen species (ROS) and Ca2+ compared to the treatment with CPT‐11 or NmAb alone. Cells that were pretreated with N‐acetyl‐l‐cysteine, a substance that scavenges ROS, and then treated with CPT‐11, NmAb, or a combination of CPT‐11 and NmAb exhibited higher numbers of viable cells compared to those treated with CPT‐11 or NmAb alone. The combination of CPT‐11 and NmAb resulted in significantly higher caspase‐3, ‐8, and ‐9 activity levels than CPT‐11 or NmAb alone, as measured by flow cytometer assay. The combination of CPT‐11 and NmAb in HeLa cells resulted in elevated endoplasmic reticulum stress‐, mitochondria‐, and caspase‐mediated proteins compared to treatment with CPT‐11 or NmAb alone. According to these observations, NmAb enhances the effectiveness of CPT‐11 in fighting cancer by stimulating cell death in the HeLa cells. Therefore, NmAb has the potential to improve the efficacy of CPT‐11 as a future cervical cancer treatment in humans.

show abstract

A Cancer-Specific Monoclonal Antibody against HER2 Exerts Antitumor Activities in Human Breast Cancer Xenograft Models

Cited by 9 publications

References 50 publications

Defucosylated Anti-CD44 Monoclonal Antibodies Exert Antitumor Activities against Esophageal Tumor Xenograft

Defucosylated Anti-CD44 Monoclonal Antibodies Exert Antitumor Activities against Esophageal Tumor Xenograft

C<sub>8</sub>Mab-21: A Novel Anti-human CCR8 Monoclonal Antibody for Flow Cytometry

Nimotuzumab and irinotecan synergistically induce ROS‐mediated apoptosis by endoplasmic reticulum stress and mitochondrial‐mediated pathway in cervical cancer

Contact Info

Product

Resources

About