P1, N=212, Recruiting, Xencor, Inc. | Not yet recruiting --> Recruiting

More importantly, CAR-NK cells combined with immune checkpoint inhibitors, anti-PD-L1, could synergistically enhance the antitumor efficacy of CLDN6-targeted CAR-NK cells. These results indicate that CLDN6-CAR NK cells possess strong antitumor activity and represent a promising immunotherapeutic modality for ovarian cancer.

P1, N=270, Recruiting, NovaRock Biotherapeutics, Ltd | Not yet recruiting --> Recruiting

Besides, CLDN6 overexpression inhibited tumor growth in vivo. In conclusion, CLDN6 inhibited NSCLC cell proliferation through inactivating aerobic glycolysis via the RIP1/ASK1/JNK axis.

P1, N=212, Not yet recruiting, Xencor, Inc.

P1, N=270, Not yet recruiting, NovaRock Biotherapeutics, Ltd

P1/2, N=288, Recruiting, BioNTech SE

Through the PDZ-binding motif (PBM), CLDN6 bound to ZO-1 to interact with PTEN, and regulate AKT/MDM2 pathway. Collectively, our data enriched the theoretical basis for CLDN6 as a potential biomarker for diagnosis, therapy and prognosis of CRC.

P1, N=98, Recruiting, Amgen | Active, not recruiting --> Recruiting | Trial completion date: Jun 2027 --> Feb 2028 | Trial primary completion date: Dec 2025 --> Apr 2026

Contrarily, upon overexpression of CDLN6, the aforementioned experimental results were reversed. CLDN6 knockdown results in the inhibition of HCC cells' infiltration and migration and promotes apoptosis via downregulation of the JAK2/STAT3 signaling pathway.

P1, N=98, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting

Additional sites will be opened in Europe, USA, and Asia in 2023. Clinical trial information: NCT05262530.

P1, N=178, Recruiting, Chugai Pharmaceutical | Not yet recruiting --> Recruiting

The data provide a new insight into the inhibitory effects of CLDN6-mediated autophagy on breast cancer metastasis, and revealed the new mechanism of CLDN6 regulating autophagy through WIP-dependent actin cytoskeleton. Our findings enrich the theoretical basis for CLDN6 as a potential biomarker for breast cancer diagnosis and therapy.

P1, N=98, Recruiting, Amgen | Not yet recruiting --> Recruiting

P1, N=178, Not yet recruiting, Chugai Pharmaceutical

P1/2, N=288, Recruiting, BioNTech SE | N=216 --> 288

P1, N=98, Not yet recruiting, Amgen | Trial completion date: Nov 2027 --> Feb 2027 | Trial primary completion date: May 2026 --> Aug 2025

We propose that CLDN6 participates in the development of GTD and may become a new therapeutic target for CC.

P1, N=98, Not yet recruiting, Amgen | Trial completion date: Jun 2027 --> Nov 2027 | Trial primary completion date: Dec 2025 --> May 2026

CLDN6 expression seems ubiquitous in all elements of GCT and is worthy of investigation as a diagnostic biomarker and therapeutic target. (Clinical trial information: NCT03760081).

In conclusion, CLDN6 suppressed ERK/Sp1/cyclin D1 and ERK/IL-8 signaling to inhibit proliferation, migration and invasion in breast cancer cells. The mechanism may provide experimental evidence for the treatment of breast cancer targeting CLDN6.

P1, N=98, Not yet recruiting, Amgen | Trial completion date: May 2026 --> Jun 2027 | Initiation date: May 2022 --> Oct 2022 | Trial primary completion date: Jul 2024 --> Dec 2025

In addition, we demonstrated that CLDN6 may inhibit the migration and invasion abilities by activating the TYK2/STAT3 pathway. Therefore, our data indicated that CLDN6 acted as a tumor suppressor and had the potential to be regarded as a biomarker for the progression of colon cancer.

P1/2, N=40, Recruiting, Second Affiliated Hospital of Guangzhou Medical University

P1/2, N=216, Recruiting, BioNTech SE | Not yet recruiting --> Recruiting

P1, N=98, Not yet recruiting, Amgen

P1/2, N=216, Not yet recruiting, BioNTech SE

CLDN6 interacted with a transcriptional co-activator with PDZ-binding motif (TAZ) and reduced the level of TAZ, thereby suppressing c-MYC transcription, which led to a reduction in glucose uptake and lactate production. Considered together, our results suggested that CLDN6 suppressed c-MYC-mediated aerobic glycolysis to inhibit the proliferation of breast cancer by TAZ, which indicated that CLDN6 acted as a novel regulator of aerobic glycolysis and provided a theoretical basis for CLDN6 as a biomarker of progression in breast cancer.

P1, N=42, Completed, Ganymed Pharmaceuticals GmbH | N=72 --> 42

Our study showed that CLDN6 and CLDN10 were prognostic biomarkers correlated with the immune microenvironment in ovarian cancer. These results reveal new roles for CLDN6 and CLDN10 as potential therapeutic targets in the treatment of ovarian cancer.

"Robust engraftment of CLDN6 CAR-T cells and first signs of efficacy could already be observed in initial dose cohort. Enrollment into higher dose levels and cohorts for combination with CARVac is currently ongoing."

Moreover, we generated evidences that TβRII KO CAR T-cells could appreciably resist the suppressive effect of iTregs on proliferation, while WT CAR T cells failed. In conclusion, genomic knock out of the TGFβRII may become a promising approach in immunotherapy of solid tumors, as it may override one of the key negative regulatory signaling pathways in T-cells.

CLDN6 may play an important role in meningioma migration and invasion, and it may serve as a novel diagnostic/prognostic biomarker as well as a potential therapeutic target.

Furthermore, CLDN6, at least in part, also regulated gene expression in an ERα-independent manner. Implications: The identification of this machinery highlights regulation of the transcription factors by cell adhesion to advance tumor progression.

Thereby, DuoBody-CD40×4-1BB provides a unique combination of priming and enhancing existing anti-tumor immunity. DuoBody-CD40×4-1BB is currently being evaluated in patients with advanced solid tumors in a first-in-human trial (NCT04083599).

Weighted correlation network analysis (WGCNA) was utilized to mine cancer biomarkers related to CD8 T cells. With the consequences of univariate Cox proportional hazards analysis and least absolute shrinkage and selection operator (LASSO) COX regression analysis, the prognostic index based on 17 methylation driver genes (ZNF677, FAM83A, TRIM58, CLDN6, NKD1, NFE2L3, FKBP5, ITGA5, ASCL2, SLC24A4, WNT3A, TMEM171, PTPRH, ITPKB, ITGA2, SLC6A17, and CCDC81) and four CD8 T cell-related genes (SPDL1, E2F7, TK1, and TYMS) was successfully established, which could make valuable predictions for the survival risk of patients with early-stage LUAD.

A de novo anti-CLDN6 monoclonal antibody conjugated with cytotoxic agent (Mertansine) DM1 (CLDN6-DM1) was developed. Preclinical data on both HCC cell lines and primary tumors showed the potent antitumor efficiency of CLDN6-DM1 as a single agent or in combination with sorafenib in HCC treatment.

P2, N=19, Completed, Astellas Pharma Global Development, Inc. | Recruiting --> Completed | N=46 --> 19 | Trial completion date: Feb 2021 --> Oct 2020 | Trial primary completion date: Feb 2021 --> Oct 2020