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"bluebird has recently announced the target (MAGE-A4) of the first TCR product candidate developed in the partnership and it plans to take the MAGE-A4 TCR product candidate into the clinic in 2020. MAGE-A4 is a member of the melanoma antigen gene (MAGE) protein family and is highly expressed in a number of cancer types (melanoma, breast, colon and ovarian) while retaining low expression in healthy tissues. One of the most advanced assets in the sector is in development by Adaptimmune, which is developing a TCR targeting MAGE-A4 (ADP-A2M4). ADP-A2M4 is being tested in a Phase I, openlabel trial in a range of cancer patients who are HLA-A*02 positive. The trial is expected to enrol 42 patients and has to date completed three dose expansion groups (100 million, 1 billion and 5 billion cells) and is in an ongoing expansion group (up to 10 billion cells). The first two cohorts (100 million and 1 billion) were in six ovarian patients and demonstrated limited efficacy (one patient initially had 27% reduction but progressed at week 12). In cohort 3 (5 billion cells) and the expansion phase (up to 10 billion cells) a total of 10 synovial patients were treated (five of whom received the maximum dose of 10 billion cells), of which 4 of 5 at the highest dose (10 billion cells) demonstrated a partial response. Responses in other tumour types to date have been minimal. Adverse events for all tumour types have been typical of patients treated with other cell therapies.
As shown by Adaptimmune?s data, selecting the correct indications and dose will be critical to the success of any MAGE-A4 TCR product. However, arguably the correct T-cell/TCR design is more important. Using Medigene?s technology, a TCR has been selected that Medigene and bluebird believe has the highest possible avidity needed to drive tumour response. In tumour xenograft models, the MAGE-A4 TCR demonstrated durable tumour elimination beyond that of a NY-ESO-1 TCR. Additionally, the TCR has been shown to be co-receptor independent and able to generate cytotoxicity in both CD8 and CD4 T-cell populations.
Both bluebird and Medigene carried out significant work to ensure limited cross-reactivity of the TCR with other antigens. In addition to selecting the correct TCR, bluebird is designing extra features into the T-cells to promote the best response in solid tumours....
...The Mage-A4 TCR is expected to enter the clinic in 2020 in a range of cancers."
- Vom begrenzten ADAP-Erfolg lernen.. Es sind offenbare mehrere MAGE-A4-Studien von BLUE geplant... Erhöht dann wohl auch die Chance auf MSt.für Medigene (Für diesen TCR dann aber sicherlich trotzdem begrenzt auf 250Mio.+ Umsatzbet.)
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