Agreed it is early days with CAR-Ts in solid tumours and there are several well known challenges, but I think it is worth considering some of the idiosyncrasies of the CHM trial.
Firstly, cells are being delivered locally to the site of the resected tumour via intraventricular administration. This means a high concentration of cells can be delivered directly to the tumour, which is in contrast to systemic administration for other solid tumours which can result in issues with trafficking and infiltration of sufficient numbers of cells to the tumour. Animal studies and early clinical studies (including the lowest dose cohorts of this study) have shown promising therapeutic response with local delivery without the need for combination therapies.
Secondly, the GBM TME is different to other non-CNS tumours (in fact is even different between different GBM molecular subtypes) and can switch in response to surgery and the rise of residual tumour initiating stem cells (TICs). As an important aside, I posted details of a publication some months ago showing TICs express the CLTX target, which gives rise to the tantalising prospect that CLTX-CAR-t cells can kill TICs which could result in cure.
Putting these 2 things together means that the CHM design has potential advantages in that the "weight of numbers" and other advantages of local delivery could overcome any TME immunosuppression in some or all of the different subtypes. Also, the first 2 dosing cohorts have shown good cell persistence.
Anyway, time will tell but I feel this has some intriguing advantages over other solid tumour programs.
CHM Price at posting:
9.9¢ Sentiment: Buy Disclosure: Held
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