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

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1941 - 1941

Опубликована: Фев. 5, 2024

Monoclonal antibody (mAb)-based and/or cell-based immunotherapies provide innovative approaches to cancer treatments. However, safety concerns over targeting normal cells expressing reactive antigens still exist. Therefore, the development of cancer-specific mAbs (CasMabs) that recognize with in vivo antitumor efficacy is required minimize adverse effects. We previously screened anti-human epidermal growth factor receptor 2 (HER2) and successfully established a anti-HER2 mAb, H

Язык: Английский

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

Oncology Reports, Год журнала: 2024, Номер 52(5)

Опубликована: Авг. 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 IgG_2a version of the anti‑pan‑CD44 mAbs (5‑mG_2a C₄₄Mab‑46‑mG_2a) evaluate antitumor activities against CD44‑positive cells. Both 5‑mG_2a C₄₄Mab‑46‑mG_2a 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 IgG_2a. These results indicate that exert cancers be promising therapeutic regimen

Язык: Английский

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Antitumor Activities of a Humanized Cancer-Specific Anti-HER2 Monoclonal Antibody, humH2Mab-250 in Human Breast Cancer Xenografts

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1079 - 1079

Опубликована: Янв. 26, 2025

Monoclonal antibody (mAb) and cell-based immunotherapies represent cutting-edge strategies for cancer treatment. However, safety concerns persist due to the potential targeting of normal cells that express reactive antigens. Therefore, it is crucial develop cancer-specific mAbs (CasMabs) can bind antigens exhibit antitumor activity in vivo, thereby reducing risk adverse effects. We previously screened human epidermal growth factor receptor 2 (HER2) successfully developed a anti-HER2 mAb, H2Mab-250/H2CasMab-2 (mouse IgG1, kappa). In this study, we assessed both vitro vivo efficacy humanized H2Mab-250 (humH2Mab-250). Although humH2Mab-250 showed lower reactivity HER2-overexpressed Chinese hamster ovary-K1 (CHO/HER2) breast cell lines (BT-474 SK-BR-3) than trastuzumab flow cytometry, similar antibody-dependent cellular cytotoxicity (ADCC) against CHO/HER2 presence effector splenocytes. addition, exhibited significant complement-dependent (CDC) compared trastuzumab. Furthermore, possesses compatible effects xenografts with These findings highlight distinct roles ADCC CDC suggest direction clinical development HER2-positive tumors.

Язык: Английский

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Anti-HER2 cancer-specific mAb, H2Mab-250-hG₁ possesses higher complement-dependent cytotoxicity than trastuzumab

Опубликована: Июль 11, 2024

Cancer-specific monoclonal antibodies (CasMabs) that recognize cancer-specific antigens with in vivo antitumor efficacy are innovative therapeutic strategies for minimizing the adverse effects. We previously established a anti-human epidermal growth factor receptor 2 (HER2)monoclonal antibody (mAb), H2Mab-250/H2CasMab-2. In flow cytometry and immunohistochemistry, H2Mab-250 reacted HER2-positive breast cancer cells but did not show reactivity to normal epithelial cells. contrast, clinically approved anti-HER2 mAb, trastuzumab, strongly recognizes both cytometry. The human IgG1 version of (H2Mab-250-hG1) possesses compatible effects against xenografts trastuzumab despite lower affinity effector activation than vitro. This study compared antibody-dependent cellular cytotoxicity (ADCC) complement-dependent (CDC) between H2Mab-250-hG1 trastuzumab. Both showed ADCC activity CHO/HER2 cell lines (BT-474 SK-BR-3) presence natural killer Some tendency was observed more significant effect H2Mab-250-hG1. Importantly, exhibited superior CDC these Similar results were obtained mouse IgG2a types These suggest different contributions activities indicate future direction clinical development tumors.

Язык: Английский

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Anti-HER2 Cancer-Specific mAb, H2Mab-250-hG1, Possesses Higher Complement-Dependent Cytotoxicity than Trastuzumab

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8386 - 8386

Опубликована: Авг. 1, 2024

Cancer-specific monoclonal antibodies (CasMabs) that recognize cancer-specific antigens with in vivo antitumor efficacy are innovative therapeutic strategies for minimizing adverse effects. We previously established a anti-human epidermal growth factor receptor 2 (HER2) antibody (mAb), H2Mab-250/H2CasMab-2. In flow cytometry and immunohistochemistry, H2Mab-250 reacted HER2-positive breast cancer cells but did not show reactivity to normal epithelial cells. contrast, clinically approved anti-HER2 mAb, trastuzumab, strongly recognizes both cytometry. The human IgG1 version of (H2Mab-250-hG1) possesses compatible effects against xenografts trastuzumab despite the lower affinity effector activation than vitro. This study compared antibody-dependent cellular cytotoxicity (ADCC) complement-dependent (CDC) between H2Mab-250-hG1 trastuzumab. Both showed ADCC activity HER2-overexpressed Chinese hamster ovary -K1 cell lines (BT-474 SK-BR-3) presence natural killer Some tendency was observed where more significant effect H2Mab-250-hG1. Importantly, exhibited superior CDC these Similar results were obtained mouse IgG2a types These suggest different contributions activities indicate future direction clinical development tumors.

Язык: Английский

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

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9190 - 9190

Опубликована: Авг. 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

Язык: Английский

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Establishment of a Highly-sensitive Anti-EphB2 Monoclonal Antibody Eb2Mab-3 for Flow Cytometry

Опубликована: Июнь 11, 2024

EphB2 is a member of the Eph family tyrosine kinase receptors. binds to ephrin-B1, ephrin-B2, and ephrin-B3, which are critical regulators vascular nervous development through controlling cell migration axon guidance. overexpressed in tumors, including glioma, breast cancer, hepatocellular carcinoma, malignant mesothelioma, it functions as tumor promoter. Therefore, monoclonal antibodies (mAbs) against essential for diagnosis therapy EphB2-positive tumors. In this study, we developed novel mAbs human using Cell-Based Immunization Screening (CBIS) method. One established anti-EphB2 mAbs, Eb2Mab-3 (mouse IgG1, kappa), reacted with EphB2-overexpressed Chinese hamster ovary-K1 (CHO/EphB2) an endogenously EphB2-expressing cancer line (LS174T) by flow cytometry. Using cytometry, dissociation constant (KD) values CHO/EphB2 LS174T were determined 1.1 × 10−9 M 3.6 10−10 M, respectively. These results indicated that possesses high affinity detecting could apply therapy.

Язык: Английский

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A Cancer-Specific Anti-Podoplanin Monoclonal Antibody, PMab-117-mG2a Exerts Antitumor Activities in Human Tumor Xenograft Models

Cells, Год журнала: 2024, Номер 13(22), С. 1833 - 1833

Опубликована: Ноя. 6, 2024

Podoplanin (PDPN) overexpression is associated with poor clinical outcomes in various tumors. PDPN involved malignant tumor progression by promoting invasiveness and metastasis. Therefore, considered a promising target of monoclonal antibody (mAb)-based therapy. Because also plays an essential role normal cells such as kidney podocytes, cancer specificity required to reduce adverse effects on cells. We developed cancer-specific mAb (CasMab) against PDPN, PMab-117 (rat IgM, kappa), immunizing rats PDPN-overexpressed glioblastoma The recombinant mouse IgG

Язык: Английский

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Molecular Biology of Cancer—Interplay of Malignant Cells with Emerging Therapies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 13090 - 13090

Опубликована: Дек. 5, 2024

Cancer is currently one of the leading causes death worldwide, and according to data from World Health Organization reported in 2020, it ranks as second cause globally, accounting for 10 million fatalities [...].

Язык: Английский

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In Silico Design of Peptide Inhibitors Targeting HER2 for Lung Cancer Therapy

Cancers, Год журнала: 2024, Номер 16(23), С. 3979 - 3979

Опубликована: Ноя. 27, 2024

Background/Objectives: Human epidermal growth factor receptor 2 (HER2) is overexpressed in several malignancies, such as breast, gastric, ovarian, and lung cancers, where it promotes aggressive tumor proliferation unfavorable prognosis. Targeting HER2 has thus emerged a crucial therapeutic strategy, particularly for HER2-positive malignancies. The present study focusses on the design optimization of peptide inhibitors targeting HER2, utilizing machine learning to identify enhance candidates with elevated binding affinities. aim provide novel options malignancies linked overexpression. Methods: This started extraction structural examination protein, succeeded by designing sequences derived from essential interaction residues. A technique (XGBRegressor model) was employed predict affinities, identifying top 20 possibilities. underwent further screening via FreeSASA methodology free energy calculations, resulting selection four primary (pep-17, pep-7, pep-2, pep-15). Density functional theory (DFT) calculations were utilized evaluate molecular reactivity characteristics, while dynamics simulations performed investigate inhibitory mechanisms selectivity effects. Advanced computational methods, QM/MM simulations, offered more understanding peptide–protein interactions. Results: Among principal peptides, pep-7 exhibited most DFT values (−3386.93 kcal/mol) maximum dipole moment (10,761.58 Debye), whereas pep-17 had lowest value (−5788.49 minimal (2654.25 Debye). Molecular indicated that steady −12.88 kcal/mol consistently bound inside pocket during 300 ns simulation. showed overall total system, which combines both QM MM contributions, remained around −79,000 ± 400 kcal/mol, suggesting entire protein–peptide complex stable state, maintaining strong, well-integrated binding. Conclusions: Pep-7 promising peptide, displaying strong stability, favorable energy, stability HER2-overexpressing cancer models. These findings suggest viable candidate offering potential treatment strategy against HER2-driven

Язык: Английский

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