Which is better, autologous CAR-T or allogeneic CAR-T? The news...

Which is better, autologous CAR-T or allogeneic CAR-T? The news that the FDA is investigating the serious risk of cancer following CAR-T treatment gives a whole new dimension to the debate. Secondary cancer is a known risk - however, who knew it? - but despite the reassurance that it is rare, the market doesn't like question marks. The fact that its now an 'investigation' turns the known risk into a risk-under-the-spotlight for clinicians, patients, the scientific community, Big Pharma and investors or Mr Market.

The FDA is investigating the serious risk of T-cell malignancy following BCMA-directed or CD19-directed autologous CAR-T immunotherapies. It appears that the cancer risk is related to viral vectors used to deliver the CAR into the T cell genome. So, just to recap, the investigation is in autologous CAR-T. But wait, allogeneic CAR-T therapies may also use viral vectors so what does it mean for azer-cel?

Its the point of differentiation that counts. It appears that the autologous method for insertion utilise lentivirus or retrovirus vectors that result in a semi-random integration of variable number resulting in heterogenous expression with the potential for insertional mutagenesis. Now that can't be good and it now appears quite obviously that its not. On the other hand, azer-cel uses the ARCUS genome editing technology to insert the CAR transgene to a defined location in the genome resulting in a consistent and safe product.

The article Integration of a CD19 CAR into the TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells by MacLeod et al published February 2017 is recommended reading.