Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Kenichiro Ishikawa
,
Hiroyuki Suzuki
* ORCID logo ,
Tomokazu Ohishi
ORCID logo ,
Guanjie Li
ORCID logo ,
Tomohiro Tanaka
,
Manabu Kawada
ORCID logo ,
Akira Ohkoshi
ORCID logo ,
Mika K. Kaneko
,
Yukio Katori
,
Yukinari Kato
* ORCID logo
Version 1 : Received: 2 August 2024 / Approved: 4 August 2024 / Online: 6 August 2024 (05:04:30 CEST)

A peer-reviewed article of this Preprint also exists.

Ishikawa, K.; Suzuki, H.; Ohishi, T.; Li, G.; Tanaka, T.; Kawada, M.; Ohkoshi, A.; Kaneko, M.K.; Katori, Y.; Kato, Y. Anti-CD44 Variant 10 Monoclonal Antibody Exerts Antitumor Activity in Mouse Xenograft Models of Oral Squamous Cell Carcinomas. Int. J. Mol. Sci. 2024, 25, 9190. Ishikawa, K.; Suzuki, H.; Ohishi, T.; Li, G.; Tanaka, T.; Kawada, M.; Ohkoshi, A.; Kaneko, M.K.; Katori, Y.; Kato, Y. Anti-CD44 Variant 10 Monoclonal Antibody Exerts Antitumor Activity in Mouse Xenograft Models of Oral Squamous Cell Carcinomas. Int. J. Mol. Sci. 2024, 25, 9190.

Abstract

CD44 regulates cell adhesion, proliferation, survival, and stemness and has been considered a tumor therapy target. CD44 possesses the shortest CD44 standard (CD44s) and a variety of CD44 variant (CD44v) isoforms. Since the expression of CD44v is restricted in epithelial cells and carcinomas compared to CD44s, CD44v has been considered a promising target for monoclonal antibody (mAb) therapy. We previously developed an anti‐CD44v10 mAb, C44Mab-18 (IgM, kappa) to recognize the variant exon 10-encoded region. In the present study, a mouse IgG2a version of C44Mab-18 (C44Mab-18-mG2a) was generated to evaluate the antitumor activities against CD44-positive cells compared with previously established anti-pan CD44 mAb, C44Mab-46-mG2a. C44Mab-18-mG2a exhibited higher reactivity compared with C44Mab-46-mG2a to CD44v3–10-overexpressed CHO-K1 (CHO/CD44v3–10) and oral squamous cell carcinoma cell lines (HSC-2 and SAS) in flow cytometry. C44Mab-18-mG2a exerted a superior antibody‐dependent cellular cytotoxicity (ADCC) against CD44v3–10. In contrast, C44Mab-46-mG2a showed a superior complement‐dependent cytotoxicity (CDC) against CD44v3–10. A similar tendency was observed in ADCC and CDC against HSC-2 and SAS. Furthermore, administering C44Mab-18-mG2a or C44Mab-46-mG2a significantly suppressed CD44v3–10, HSC-2, and SAS xenograft tumor growth compared with the control mouse IgG2a. These results indicate that C44Mab-18-mG2a could be a promising therapeutic regimen for CD44v10-positive tumors.

Keywords

CD44 variant 10; monoclonal antibody; ADCC; CDC; oral cancer; antitumor activity

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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