MAGEA4 (Melanoma antigen family A, 4)

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

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.