MAGEA4 (Melanoma antigen family A, 4)

Furthermore, MAGED4 contributes to the downregulation of suppressor of cytokine signaling 3 (SOCS3) via TRIM21, and this effect can be partially reversed by si-TRIM21 in MAGED4-overexpressing cells. These findings indicate that MAGED4 promotes HCC progression through the activation of the JAK2/STAT3 pathway by stabilizing TRIM21, suggesting that targeting MAGED4 may provide new insights into HCC treatment strategies.

Six prognostic genes, particularly RAB25 and PLAU, influence ESCC progression and immune microenvironment remodeling.

No further DLTs occurred in the RP2D range with dexamethasone premedication. These findings show that the bispecific TCER platform has a manageable safety profile with mostly transient adverse events and promising antitumor activity at the RP2D of IMA401 with or without pembrolizumab. ClinicalTrials.gov identifier: NCT05359445 .

P1, N=9, Recruiting, Zelluna Immunotherapy AS

NY-ESO-1 is the most prominent target, followed by MAGE-A4, KRAS, PRAME, HPV16 E6/E7, and HBV surface antigen, with letetresgene autoleucel and LioCyx-M004 being the most investigated TCR-T products. Collectively, TCR-T therapy is a promising field in tumor immunotherapy with continuous research investment and advancing clinical progress.

The recent US FDA approvals of lifileucel (a TIL therapy for advanced melanoma) and afamitresgene autoleucel (a TCR therapy targeting MAGE-A4 in synovial sarcoma) mark the first regulatory recognition of cell therapies for solid tumours and signal a new era for oncology...Emphasis is placed on emerging innovations like gene-edited and allogeneic therapies, as well as future directions for integrating cell therapies into mainstream oncology. We conclude with recommendations for overcoming barriers related to cost, toxicity management, and equitable access across Europe.

These findings highlight that MAGEA4 may contribute to neuroendocrine differentiation and survival in prostate cancer cells, and may represent a potential therapeutic vulnerability in aggressive prostate cancers.

These skin-related adverse events, which appeared in contradiction to the initial in vitro results in skin co-culture models, were hypothesized to be driven by the target-independent activation capability of the UCHT1-based CD3 binder, potentially enhanced in patients with a systemic pro-inflammatory profile. This study provides a translational framework for TCR-based immunotherapies, demonstrating the successful application of NAMs to define a safe starting dose while highlighting the critical need for refining these methodologies to accurately predict complex, systemic immune-related adverse events, particularly those involving barrier organs.

P1/2, N=100, Recruiting, Shenzhen Geno-Immune Medical Institute | Unknown status --> Recruiting | Trial completion date: Dec 2021 --> Dec 2028 | Trial primary completion date: Jun 2021 --> Jun 2028

P1/2, N=100, Recruiting, Shenzhen Geno-Immune Medical Institute | Unknown status --> Recruiting | Trial completion date: Dec 2021 --> Dec 2029 | Trial primary completion date: Jun 2021 --> Jun 2028

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