A Humanized and Defucosylated Antibody against Podoplanin (humLpMab-23-f) Exerts Antitumor Activities in Human Lung Cancer and Glioblastoma Xenograft Models

Suzuki, Hiroyuki; Ohishi, Tomokazu; Kaneko, Mika K.; Kato, Yukinari

doi:10.3390/cancers15205080

Cited by 4 publications

(4 citation statements)

References 36 publications

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“…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

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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.

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Section: Discussionmentioning

confidence: 94%

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

Ishikawa,

Suzuki,

Ohishi

et al. 2024

Preprint

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“…We developed CasMabs against podoplanin (LpMab-2 and LpMab-23 [30]), podocalyxin (PcMab-6 [31]), and HER2 (H 2 Mab-250 [22]) by evaluating the reactivity against cancer and normal cells in flow cytometry. We also showed the in vivo antitumor effect of the recombinant mAbs (mouse IgG 2a or human IgG 1 types) derived from the abovementioned mAbs [30][31][32]. In this study, we evaluated the antitumor effect of H 2 Mab-250-mG 2a and H 2 Mab-250-hG 1 , which exhibited a cancer specificity compared to tras-mG 2a and trastuzumab, respectively (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

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

Kaneko,

Suzuki,

Ohishi

et al. 2024

IJMS

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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 cancer-specific antigens with in vivo antitumor efficacy is required to minimize the adverse effects. We previously screened anti-human epidermal growth factor receptor 2 (HER2) mAbs and successfully established a cancer-specific anti-HER2 mAb, H2Mab-250/H2CasMab-2 (IgG1, kappa). In this study, we showed that H2Mab-250 reacted with HER2-positive breast cancer cells but did not show reactivity to normal epithelial cells in flow cytometry. In contrast, a clinically approved anti-HER2 mAb, trastuzumab, recognized both breast cancer and normal epithelial cells. We further compared the affinity, effector activation, and antitumor effect of H2Mab-250 with trastuzumab. The results showed that H2Mab-250 exerted a comparable antitumor effect with trastuzumab in the mouse xenograft models of BT-474 and SK-BR-3, although H2Mab-250 possessed a lower affinity and effector activation than trastuzumab in vitro. H2Mab-250 could contribute to the development of chimeric antigen receptor-T or antibody–drug conjugates without adverse effects for breast cancer therapy.

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“…[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

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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.

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A Humanized and Defucosylated Antibody against Podoplanin (humLpMab-23-f) Exerts Antitumor Activities in Human Lung Cancer and Glioblastoma Xenograft Models

Cited by 4 publications

References 36 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

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

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

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