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Microbes & Immunity A novel anti-EphA8 monoclonal antibody

has been reported in cancers. 22,23,25 EphA8 TK-dependent numbers: JP24am0521010 (to Y. Kato), JP24ama121008
activation appears to be essential for its function. For (to Y. Kato), JP24ama221339 (to Y. Kato), JP24bm1123027
example, Tyr-phosphorylated EphA8 regulates cell-cell (to Y. Kato), and JP24ck0106730 (to Y. Kato), and by the
adhesion by interacting with Fyn. In breast cancer, EphA8 Japan Society for the Promotion of Science Grants-in-Aid
11
suppresses cell apoptosis via Akt activation and correlates for Scientific Research (KAKENHI) under grant numbers:
with poor prognosis. In addition, EphA8 expression may 22K06995 (to H. Suzuki), 24K18268 (to T. T.), 24K11652
25
mediate the resistance to paclitaxel treatment. In gastric (to H. Satofuka), and 25K10553 (to Y. Kato).
25
cancer, EphA8 promotes malignancy through Akt signaling
and interaction with a disintegrin and metalloproteinase Conflict of interest
domain-containing protein 10. In OTSCC patients, The authors declare that they have no conflict of interest
24
EphA8 expression significantly correlates with tumor, node,
metastasis stage, but not with other risk factors such as Author contributions
age, gender, drinking, and smoking history. Since EphA8 Conceptualization: Mika K. Kaneko, Yukinari Kato
22
has been reported to cooperate with stem cells, further Formal analysis: Tomohiro Tanaka
26
evaluation of its relationship with other membrane protein Funding acquisition: Tomohiro Tanaka, Hiroyuki Satofuka,
markers such as CD44 and CD133 may be valuable. 33,34 Hiroyuki Suzuki, Yukinari Kato
To analyze the population of EphA8-expressing cancer Investigation: Tomohiro Tanaka, Haruto Yamamoto, Yu
cells, detecting naïve EphA8 on these cells is necessary. Kaneko, Keisuke Shinoda, Takuya Nakamura, Guanjie
Because Ea Mab-9 recognizes EphA8 with high affinity, Li, Shiori Fujisawa, Hiroyuki Satofuka
8
it will be helpful for diagnosis and experiments using Methodology: Mika K. Kaneko
flow cytometry. However, the suitability of Ea Mab-9 for Writing – original draft: Tomohiro Tanaka
8
immunofluorescence or immunohistochemistry has not Writing – review & editing: Hiroyuki Suzuki, Yukinari Kato
yet been investigated. If unsuitable for these applications,
identifying EphA8-expressing cells in tissue samples may Ethics approval and consent to participate
be challenging.
All animal experiments were approved by the Animal Care
Eph receptors have been widely studied in the context of and Use Committee of Tohoku University (Permit number:
cancer and are gaining attention as therapeutic targets. 2022MdA-001).
2,35
Clinical trials have been conducted for various modalities,
including compounds, antibody drugs, and chimeric Consent for publication
antigen receptor (CAR)-T cells targeting Eph receptors Not applicable.
and ephrin ligands such as EphA2, EphA3, EphA5, EphB4,
ephrin A4, and ephrin B2. However, there are currently Availability of data
2,21
no drugs approved specifically for Eph receptors or ephrin
36
37
ligands. Given that mAbs against HER2, podoplanin, The data of this study are available in the article.
38
and podocalyxin established using the CBIS method have Further disclosure
revealed applicability in CAR-T therapy, it is worthwhile
to investigate the potential application of Ea Mab-9 for The paper has been uploaded to a preprint server (DOI:
8
CAR-T therapy targeting EphA8-positive tumors. 10.20944/preprints202412.1044.v1).
5. Conclusion References
Ea Mab-9, established using the CBIS method, may serve 1. Tuzi NL, Gullick WJ. Eph, the largest known family of putative
8
as a valuable tool for analyzing EphA8-related biological growth factor receptors. Br J Cancer. 1994;69(3):417-421.
responses by flow cytometry, owing to its high affinity and doi: 10.1038/bjc.1994.77
specificity. 2. Pasquale EB. Eph receptors and Ephrins in cancer
Acknowledgments progression. Nat Rev Cancer. 2024;24(1):5-27.
doi: 10.1038/s41568-023-00634-x
None.
3. Pasquale EB. Eph-ephrin bidirectional signaling in
Funding physiology and disease. Cell. 2008;133(1):38-52.

This research was supported in part by the Japan Agency doi: 10.1016/j.cell.2008.03.011
for Medical Research and Development under grant 4. Hruska M, Dalva MB. Ephrin regulation of synapse

Volume 2 Issue 4 (2025) 157 doi: 10.36922/MI025060010