P1, N=66, Recruiting, Chiome Bioscience Inc. | N=50 --> 66 | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

P2, N=35, Active, not recruiting, Beth Israel Deaconess Medical Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

CBA-1205 was well tolerated, showing no severe toxicity in patients with advanced or recurrent solid tumors. The favorable safety profile and indications of potential activity support further investigation in Parts 2 and 3 of this Phase I study to evaluate the safety, tolerability, and preliminary efficacy of CBA-1205.

P1, N=50, Recruiting, Chiome Bioscience Inc.

This study presents DLK1 as a novel biomarker in ACC with opportunities for use in the diagnosis, prognosis and longitudinal follow up of patients. DLK1, a marker of adrenocortical stem cells, is re-expressed in ACC, is measurable in patients' serum and is associated with increased malignancy.

Pharmacological intervention targeting DNA methylation combined with histone deacetylation restored ncRNA expression. These results contribute to the understanding of the epigenetic mechanisms controlling the DLK1-DIO3 region in thyroid cancer, highlighting the combined role of DNA methylation and histone marks in regulating the locus' expression.

P2, N=35, Active, not recruiting, Beth Israel Deaconess Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Jul 2023 --> Sep 2024

Overall, our results shed light on the role of the DLK1-DIO3 region, which harbors promising tumor suppressor miRNAs in thyroid cancer, and open prospects for the functional exploration of these miRNAs as therapeutic targets for PTC.

In this study, we highlight miRNAs from the Dlk1-Dio3 and miR-224/452 clusters which may be expressed cell autonomously and have expression that is associated with cell state genes in glioblastoma, most prominently in neural progenitor-like and mesenchymal-like states respectively. These findings implicate these miRNA clusters as potential regulators of glioblastoma intra-tumoral heterogeneity and may serve as valuable biomarkers for cell state identification.

We found that TRIM67 altered the behaviour of non-small cell lung cancer (NSCLC) cells by ubiquitinating DLK1 via its RING domain, which in turn activates the Notch pathway. Taken together, these findings indicate that TRIM67 may be involved in promoting the growth of NSCLC.

Therefore, the DLK1/DIO3 locus is an essential determinant of FoxM1-dependent cell proliferation during β-catenin-driven liver tumorigenesis. Targeting the DLK1-WRE enhancer to silence the DLK1/DIO3 locus might thus represent an interesting therapeutic strategy to restrict tumor growth in primary liver cancers with CTNNB1 mutations.

Our pre-clinical data demonstrate the αDC1 vaccine's ability to induce anti-tumor effects by facilitating cytotoxic T lymphocyte activity and ablating the tumor vasculature. This work, overall, provides a foundation to further interrogate immune-mediated mechanisms of protection in order to help devise efficacious αDC1-based strategies for patients with CRC.