MAGEA4 expression

P2, N=52, Active, not recruiting, Adaptimmune | Recruiting --> Active, not recruiting | N=120 --> 52

Examples are the tyrosine kinase inhibitors avapritinib and ripretinib in gastrointestinal stromal tumours (GIST), the immune check point inhibitor atezolizumab in alveolar soft part tissue sarcoma, the γ-secretase inhibitor nirogacestat in desmoid tumours, the NTRK inhibitors larotrectinib and entrectinib in tumours with NTRK fusions, the mTOR inhibitor nab-sirolimus in PEComa, and the EZH-2 inhibitor tazemetostat in epithelioid sarcoma...The challenges in drug development in soft tissue sarcoma are due to the rarity and the molecular heterogeneity of the disease and the fact that many subtypes are associated with complex karyotypes or non-targetable molecular alterations. We believe that progress maybe possible with a better understanding of the complex biology, the development of novel compounds for difficult targets such as proteolysis targeting chimeras (Protacs), the utilisation of modern clinical trial designs, and enhanced collaboration of academia with industry to develop treatments with a strong biologic rationale.

In conclusion, the E701U Ab showed reliable specificity for MAGE-A4 expression among MAGE family genes. Patients with MAGE-A4(+) BC have an unfavorable prognosis and represent potential candidates for MAGE-A4-specific immunotherapy.

P2, N=66, Active, not recruiting, Adaptimmune | Recruiting --> Active, not recruiting

In conclusion, MAGEA4-AS1-p53 complexes bind to MK2 promoter, enhancing the transcription of MK2 and activating the downstream signaling pathways, consequently promoting the proliferation and metastasis of OSCC cells. MAGEA4-AS1 may serve as a diagnostic marker and therapeutic target for OSCC patients.

Among MAGE-As, MAGE-A4 had the highest prevalence (65%), followed by MAGE-A10 (15%) and MAGE-A9 (13%)...Complementary immunohistochemical analyses were used to establish the positive correlation between RNA and protein expression for MAGE-A4 and NY-ESO-1. These data inform the strategy for optimal coverage of the SyS patient population with T-cell therapies, offering patients with SyS new options for single or combined second lines of treatment.

P2, N=3, Terminated, Adaptimmune | N=45 --> 3 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Apr 2023; Study was terminated due to difficulty recruiting subjects and lack of efficacy

Afami-cel treatment resulted in durable responses in heavily pre-treated patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. This study shows that T-cell receptor therapy can be used to effectively target solid tumours and provides rationale to expand this approach to other solid malignancies.

P1/2, N=20, Recruiting, Adaptimmune | Not yet recruiting --> Recruiting

P1, N=120, Recruiting, Adaptimmune | Trial primary completion date: Sep 2023 --> Dec 2025

P1, N=50, Recruiting, Immatics Biotechnologies GmbH | Phase classification: P1a/1b --> P1

Preliminary in vivo investigations revealed a significant deceleration in tumor growth, highlighting the therapeutic potential of these TCR-like CAR-T cells. Further investigations are warranted to validate these revelations fully and harness the complete potential of TCR-like CAR-T cells in overcoming cancer's resilient defenses.