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Microbes & Immunity Anti-mouse CXCR5 monoclonal antibody

exhausted CD8+ T cells, which can respond to immune Acknowledgments
checkpoint inhibitor therapy in tumors. Furthermore,
66
CD8+ T cells with high PD-1 expression in tumors secrete None.
high levels of CXCL13. This CXCL13 secretion attracts Funding
67
67
Tfh cells and B cells to the tumor microenvironment.
As a result, CXCL13 can predict the response to immune This research was supported in part by Japan Agency for
checkpoint inhibitor therapy that correlates with durable Medical Research and Development (AMED) under Grant
responses and increased overall survival. Therefore, Numbers: JP24am0521010 (to Y.K.), JP24ama121008 (to
67
CXCL13 and CXCR5 are novel biomarkers for predicting Y.K.), JP24ama221339 (to Y.K.), JP23am0401013 (to Y.K.),
responses to immune checkpoint inhibitor therapy. 68 JP24bm1123027 (to Y.K.), and JP24ck0106730 (to Y.K.),
and by the Japan Society for the Promotion of Science
In human breast cancer cell lines, an inverse correlation (JSPS) Grants-in-Aid for Scientific Research (KAKENHI)
between the p53 tumor suppressor and CXCR5 expression grant nos. 22K06995 (to H.S.) and 22K07224 (to Y.K).
has been reported. Silencing p53 in MCF7 cells increases
69
CXCR5 expression, which potentiates CXCL13-mediated Conflict of interest
chemotaxis. A CXCR5 promoter analysis revealed that
69
p53 suppresses the transcriptional activity of NF-κB, The authors declare that they have no competing interests.
which is important for the upregulation of CXCR5. Author contributions
69
Similarly, related tumor suppressors p63 and p73 regulate
CXCR5 through comparable mechanisms. Since CXCL13 Conceptualization: Mika K. Kaneko, Yukinari Kato
70
is one of the overexpressed chemokines in breast cancer Formal analysis: Kenichiro Ishikawa
tissues compared with normal breast tissues, mAb Investigation: Kenichiro Ishikawa, Hiroyuki Suzuki,
therapies targeting CXCR5 could be an important strategy Tomohiro Tanaka
in treating tumors. We previously modified the isotype Methodology: Mika K. Kaneko
70
of mAbs to mouse IgG to enable antibody-dependent Writing–original draft: Kenichiro Ishikawa
2a
cellular cytotoxicity (ADCC) and evaluated their antitumor Writing–review & editing: Hiroyuki Suzuki, Yukinari Kato
activities in mouse xenograft models. 71-73 Since the isotype Ethics approval and consent to participate
of Cx Mab-3 is rat IgG , an isotype switch to mouse IgG
5
2a
2b
will be required in future studies. All animal experiments were approved by the Animal Care
and Use Committee of Tohoku University (Permit number:
The CXCL13/CXCR5 axis is involved in the 2022MdA-001).
progression of autoimmune and inflammatory diseases.
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In inflammatory bowel disease (IBD), CXCL13 levels are Consent for publication
elevated in both humans and mouse models. In IBD
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patients, serum CXCL13 concentrations are significantly Not applicable.
higher than that in healthy controls. Similarly, in a mouse Availability of data
74
model of dextran sodium sulfate-induced colitis, elevated
CXCL13 levels were observed in the colon. The CXCL13 The data presented in this study are available in the article.
deficiency inhibits the occurrence and development of
the colitis and restricts CD4+CXCR5+ T cells migration Further disclosure
to mesenteric lymph nodes, resulting in an increase of The paper has been uploaded to a preprint server (doi:
regulatory B cells in the colon. Therefore, antagonizing 10.20944/preprints202410.0497.v1).
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the CXCL13/CXCR5 axis may work as a potential
therapeutic strategy for patients with IBD. Cx Mab-3 could References
5
contribute to the preclinical study through antagonizing 1. Nelson PJ, Krensky AM. Chemokines, chemokine receptors,
the CXCL13/CXCR5 axis or depleting CXCR5+ T cells. and allograft rejection. Immunity. 2001;14(4):377-386.
As such, Cx Mab-3 may be useful for establishing proof of doi: 10.1016/s1074-7613(01)00118-2
5
concept in preclinical studies. 71-73
2. Lukacs-Kornek V, Engel D, Tacke F, Kurts C. The role of
5. Conclusion chemokines and their receptors in dendritic cell biology.
Front Biosci. 2008;13:2238-2252.
Cx Mab-3 is useful for detecting mCXCR5 by flow
5
cytometry with high affinity and may be useful for doi: 10.2741/2838
establishing proof of concept in preclinical studies. 3. Bonecchi R, Galliera E, Borroni EM, et al. Chemokines and

Volume 2 Issue 1 (2025) 109 doi: 10.36922/mi.5664