EphB2-Targeting Monoclonal Antibodies Exerted Antitumor Activities in Triple-Negative Breast Cancer and Lung Mesothelioma Xenograft Models

Our plain-English summary of EphB2-Targeting Monoclonal Antibodies Exerted Antitumor Activities in Triple-Negative Breast Cancer and Lung Mesothelioma Xenograft Models, by R. Ubukata, T. Ohishi, M.K. Kaneko, et al (International Journal of Molecular Sciences, 2025).

The study

• Authors: R. Ubukata, T. Ohishi, M.K. Kaneko, H. Suzuki, Y. Kato
• Journal: International Journal of Molecular Sciences
• Published: 2025;26(17)
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Eph receptor B2 (EphB2) overexpression is associated with poor clinical outcomes in various tumors. EphB2 is involved in malignant tumor progression through the promotion of invasiveness and metastasis. Genetic and transcriptome analyses implicated that EphB2 is a therapeutic target for specific tumor types. A monoclonal antibody (mAb) is one of the essential therapeutic strategies for EphB2-positive tumors. We previously developed an anti-EphB2 mAb, Eb2Mab-12 (IgG1, kappa), by immunizing mice with EphB2-overexpressed glioblastoma. Eb2Mab-12 specifically reacted with the EphB2-overexpressed Chinese hamster ovary-K1 (CHO/EphB2) and some cancer cell lines in flow cytometry. In this study, we engineered Eb2Mab-12 into a mouse IgG2a type (Eb2Mab-12-mG2a) and a human IgG1-type (Eb2Mab-12-hG1) mAb. Eb2Mab-12-mG2a and Eb2Mab-12-hG1 retained the reactivity to EphB2-positive cells and exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in the presence of effector cells and complements, respectively. In CHO/EphB2, triple-negative breast cancer, and lung mesothelioma xenograft models, both Eb2Mab-12-mG2a and Eb2Mab-12-hG1 exhibited potent antitumor efficacy. These results indicated that Eb2Mab-12-derived mAbs could be applied to mAb-based therapy against EphB2-positive tumors.

In plain English

This was a laboratory and mouse experiment, not a study of people. The authors took an existing anti-EphB2 mouse IgG1 antibody (Eb2Mab-12) and re-engineered it into a mouse IgG2a form (Eb2Mab-12-mG2a) and a human IgG1 form (Eb2Mab-12-hG1). By flow cytometry both forms bound EphB2-overexpressing CHO cells, the triple-negative breast cancer line MDA-MB-231 and the lung mesothelioma line NCI-H226, but not parental CHO-K1 or EphB2-knockout LS174T cells. With mouse splenocytes as effector cells, Eb2Mab-12-mG2a gave 16.8% versus 6.5% cytotoxicity against NCI-H226 and Eb2Mab-12-hG1 gave 12.5% versus 4.6% (both p less than 0.05), with similar significant results for complement-dependent cytotoxicity and for MDA-MB-231. In BALB/c nude mice given 100 micrograms of antibody intraperitoneally twice, final xenograft weights were lower than in the corresponding control-IgG groups by 29% (mG2a) and 33% (hG1) for NCI-H226, 33% and 23% for MDA-MB-231, and 87% and 77% for CHO/EphB2. Against LS174T, neither antibody gave significant ADCC or an obvious antitumour effect, though Eb2Mab-12-hG1 gave significant CDC. The authors concluded these antibodies could be applied to antibody-based therapy against EphB2-positive tumours.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: laboratory cell-line experiments (flow cytometry, ADCC, CDC) with mouse xenograft antitumour experiments
• Who was studied: Human cancer cell lines (MDA-MB-231 triple-negative breast cancer, NCI-H226 lung mesothelioma, LS174T colorectal cancer) and CHO-K1/CHO-EphB2 cells, plus female BALB/c nude mice (4 weeks old) bearing subcutaneous xenografts, 8 mice per treatment group; work done in Japan (animal approvals dated 2025)
• Exposure: Treatment with the engineered anti-EphB2 antibodies Eb2Mab-12-mG2a (mouse IgG2a) or Eb2Mab-12-hG1 (human IgG1), 100 micrograms given intraperitoneally on day 8 and day 14 (day 7 and 14 for NCI-H226), compared with control mouse IgG2a or human IgG1; in vitro assays used 100 micrograms/mL
• Main results:
  • Against the lung mesothelioma line NCI-H226, antibody-dependent cellular cytotoxicity was 16.8% for Eb2Mab-12-mG2a versus 6.5% for control mouse IgG2a, and 12.5% for Eb2Mab-12-hG1 versus 4.6% for control human IgG1 (both p less than 0.05)
  • Complement-dependent cytotoxicity against NCI-H226 was 12.1% for Eb2Mab-12-mG2a versus 5.4% for control mouse IgG2a, and 7.4% for Eb2Mab-12-hG1 versus 1.6% for control human IgG1 (both p less than 0.05)
  • In NCI-H226 xenograft-bearing mice, xenograft weight was 29% lower with Eb2Mab-12-mG2a and 33% lower with Eb2Mab-12-hG1 than in the corresponding control-IgG groups (both p less than 0.01), with tumour volume significantly reduced on day 21
  • In MDA-MB-231 (triple-negative breast cancer) xenografts, xenograft weight was 33% lower with Eb2Mab-12-mG2a and 23% lower with Eb2Mab-12-hG1 than in the corresponding control groups (both p less than 0.05)
  • In CHO/EphB2 xenografts, xenograft weight was 87% lower with Eb2Mab-12-mG2a and 77% lower with Eb2Mab-12-hG1 than in controls (both p less than 0.01); no body weight loss was seen in treated mice
  • Against the colorectal line LS174T, no significant ADCC by either antibody and no CDC by Eb2Mab-12-mG2a were seen; only Eb2Mab-12-hG1 gave significant CDC, and no obvious antitumour activity was seen in the LS174T xenograft
• The authors' conclusion: The authors concluded that antibodies derived from Eb2Mab-12 could be used in antibody-based therapy directed at EphB2-positive tumours
• Limitations the authors state:
  • The authors state the neutralising effect of Eb2Mab-12 has not been tested and further study is needed, including whether cell death actually occurred in treated xenografts
  • The authors note Eb2Mab-12 is not suitable for immunohistochemistry, so another antibody would be needed to detect EphB2 in tissue
  • The authors state that with their method the antibody-driven immune response could not keep pace with the fast-growing LS174T xenograft

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Monoclonal Antibody, Mesothelioma, Metastasis.

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