MAGEA4 (Melanoma antigen family A, 4)

UHRF1 loss derepresses DNA-methylation-silenced tumor antigens, including MAGE-A4, highlighting a potential vulnerability that could be leveraged therapeutically. Together, these findings connect RB1 loss with chromatin repression, lineage control, and immune exclusion, highlighting UHRF1-dependent repression as a therapeutic vulnerability in SCLC.

P1, N=95, Active, not recruiting, Immatics Biotechnologies GmbH | Recruiting --> Active, not recruiting | Trial primary completion date: Nov 2025 --> Mar 2026

P1, N=120, Active, not recruiting, USWM CT, LLC | Trial primary completion date: Apr 2026 --> Dec 2026

Seven patients had a significant reduction of the residual mass and no tumor progression, and 3 patients did not respond to the treatment and died from the disease progression. CoM mostly occurs in the unilateral eye of middle-aged and elderly patients, more common at the bulbar conjunctiva and fornix conjunctiva, and histopathological epithelial cell types are the main types, with a high recurrence and metastasis rate.

P1, N=15, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Furthermore, ADSCs-Exos increase organoid viability and confirm key protein changes. These findings demonstrate that ADSCs-Exos promote EC progression via the MAGED4B/CDH1/EMT axis.

The NY-ESO-1/MAGEA4 immune pathway may play a more prominent role than the PD-1/PD-L1 checkpoint pathway within the tumor microenvironment of DT.

P1, N=120, Active, not recruiting, USWM CT, LLC | Trial primary completion date: Dec 2025 --> Apr 2026

This study, to our knowledge, is the largest pretreatment autoantibody screen in melanoma immunotherapy, demonstrates that serum autoantibody profiles can stratify patients at risk for irAEs and ir-colitis. The identified signatures connect tumor-related and immunity-related antigens, stress-response pathways, and autoimmune mechanisms. Pretreatment autoantibody profiling offers a promising biomarker-driven approach for individualizing risk assessment, improving patient selection, and guiding early intervention strategies to enhance the safety of immune checkpoint blockade in melanoma. Beyond toxicity prediction, our findings also suggest that specific autoantibodies may reflect underlying immune activation states linked to therapeutic response.

Two cell-based modalities can target pHLA-expressing tumors: T cell receptors (TCRs) or TCR-mimetic (TCRm) antibodies reformatted as chimeric antigen receptors (CARs)...Insufficient TCR-T cell durability was overcome by coengaging 41BB or IL-2 signaling pathways, thereby enhancing tumor control in vivo. These data establish differential activities of human TCR-T and CAR-T cells targeting the same pHLA and inform the development of optimal targeting strategies to induce durable clinical responses.

This constituted only the second approval of a cell therapy in a solid tumor following lifileucel in melanoma and demonstrated the potential of cell therapies in sarcomas...However, the broader application of these therapies is hindered by the lack of targetable sarcoma-restricted immunogenic epitopes, spatiotemporal intratumoral heterogeneity, and a profoundly immunosuppressive tumor microenvironment that impedes effector-cell trafficking, expansion and persistence. While cell therapies hold promise for integration into precision medicine approaches for sarcomas, their successful implementation will require careful evaluation of clinical feasibility, logistical considerations and cost-effectiveness to optimize patient outcomes.

Clinical outcomes correlated with peripheral expansion of functional TAA-targeted T cell clones and treatment-emergent antigen spreading. Thus, further investigation of this approach, either as a single agent or combined with other complementary modalities, is warranted (ClinicalTrials.gov identifier: NCT03192462 ).