CD44v6, STn &amp; O-GD2: promising tumor associated antigens paving the way for new targeted cancer therapies

Lodewijk, Iris; Dueñas, Marta; Paramio, Jesus M.; Rubio, Carolina

doi:10.3389/fimmu.2023.1272681

Cited by 6 publications

(2 citation statements)

References 173 publications

(219 reference statements)

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“…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]. Among them, the 4C8 mAb recognizes aberrantly O-glycosylated CD44v6 with Tn (GalNAc1-O-Ser/Thr) antigen.…”

Section: Discussionmentioning

confidence: 98%

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: 98%

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

Ishikawa,

Suzuki,

Ohishi

et al. 2024

Preprint

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“…Consequently, therapeutic approaches targeting truncated O-glycans have surfaced, suggesting potential relevance in the future treatment of esophageal adenocarcinoma. A range of promising active compounds falls within different categories, encompassing antibodies [52], antibody-drug conjugates [53], CAR T cells [54][55][56], and sialidases [57].…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Analysis of Tn and STn Antigen Expression in Esophageal Adenocarcinoma

Mercanoglu,

Karstens,

Giannou

et al. 2024

Cancers

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Differential glycosylation, marked by the presence of truncated O-glycans, is a distinctive feature of epithelial-derived cancers. However, there is a notable gap in research regarding the expression of Tn and STn antigens in esophageal adenocarcinoma (EAC). To address this, we employed commercially available antibodies, previously validated for Tn and STn antigens, to analyze two cohorts of EAC tissues. Initially, large-area tissue sections from formalin-fixed paraffin-embedded (FFPE) EAC and corresponding healthy tissues were subjected to immunohistochemistry (IHC) staining and scoring. Subsequently, we evaluated the RNA expression levels of crucial O-glycosylation related genes—C1GALT1 and C1GALT1C1—using a quantitative real-time polymerase chain reaction (qRT-PCR). In a comprehensive analysis, a substantial cohort of EAC tissues (n = 311 for Tn antigen, n = 351 for STn antigen) was investigated and correlated with clinicopathological data. Our findings revealed that Tn and STn antigens are highly expressed (approximately 71% for both) in EAC, with this expression being tumor-specific. Notably, Tn antigen expression correlates significantly with the depth of tumor cell infiltration (p = 0.026). These antigens emerge as valuable markers and potential therapeutic targets for esophageal adenocarcinoma.

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Targeting CD44 and other pleiotropic co-receptors as a means for broad inhibition of tumor growth and metastasis

Mehner,

Munoz-Sagredo,

Sonnentag

et al. 2024

Clin Exp Metastasis

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Although progress has been made in the treatment of cancer, particularly for the four major types of cancers affecting the lungs, colon, breast and prostate, resistance to cancer treatment often emerges upon inhibition of major signaling pathways, which leads to the activation of additional pathways as a last-resort survival mechanism by the cancer cells. This signaling plasticity provides cancer cells with a level of operational freedom, reducing treatment efficacy. Plasticity is a characteristic of cancer cells that are not only able to switch signaling pathways but also from one cellular state (differentiated cells to stem cells or vice versa) to another. It seems implausible that the inhibition of one or a few signaling pathways of heterogeneous and plastic tumors can sustain a durable effect. We propose that inhibiting molecules with pleiotropic functions such as cell surface co-receptors can be a key to preventing therapy escape instead of targeting bona fide receptors. Therefore, we ask the question whether co-receptors often considered as “accessory molecules” are an overlooked key to control cancer cell behavior.

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CD44v6, STn & O-GD2: promising tumor associated antigens paving the way for new targeted cancer therapies

Cited by 6 publications

References 173 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 Comprehensive Analysis of Tn and STn Antigen Expression in Esophageal Adenocarcinoma

Targeting CD44 and other pleiotropic co-receptors as a means for broad inhibition of tumor growth and metastasis

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