"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.)