The new pioneer in CAR-T therapy

Now the dust has settled that CAR-therapy is definitely effective at least in treating hematologic malignancies. Novartis has won the gold metal by securing the first ever approval of its CAR-T product and Kite will soon to follow. While it is revolutionary in cancer treatment, it has its own limitation and challenges, mostly the difficulties in harvesting the useable T cells from the patient and then genetically modify them before infusing back into the patient’s body. It is a very time and labor-consuming process and therefore is very difficult to be widely used like other medications that can be simply swollen or injected. That’s why it costs so much and will be limited in use with the current modality. But as with any innovation, it will evolve and be modified to be more use-friendly as long as it is proved to be useful and I have no doubt that CAR-T therapy will see a lot of more innovative changes as the time goes by. One of the innovative explorations is to try to collect the T cells from the healthy donors, modify them and make them ready for use for patients. If this proves to be successful, CAR-T therapy will become something similar to other traditional medicines that are easily accessible to patients when needed.

 

Cellectis (CLLS), a France-based biotech, is one of a handful of companies at the forefront of so-called allogeneic CAR T-cell therapies, i.e. it uses mass production of compatible T cells from donors rather than individually modifying cells for each patient. If you want to be a visionary in investment, you got to be a bit thinking ahead. I’m excited about this new technology but with the understanding that its path to success won’t be easy and smooth. CLLS is indeed facing some significant challenges at the moment.

 

After its initial promising result from an 11 year girl with aggressive acute lymphoblastic leukaemia (ALL) with its wholly-owned candidate, UCART19, the company has already licensed it to Pfizer and Servier. Unfortunately its first Phase I trial is just being put on hold due to the death of a patient. As we all know now for the current autologous CAR-T therapy (using self T cells), it may induce a life-threatening side effect, cytokine release syndrome (CRS). While it sounds exciting by using the allogenic T cells (from others), it faces a lot more challenges associated with this foreign source of cells. You see, CAR-T therapy is very similar to the organ transplantation in the sense that it is much safer to use one’s own tissue (if possible) than to use other’s tissue. With the allogenic CAR-T therapy, it is not only susceptible to the same type of CRS, it may also be associated with other life-threatening side effects that the autologous CAR-T is not prone to, namely the capillary leak syndrome (CLS), graft versus host disease, and other autoimmune reactions. All of them could be fatal if not managed appropriately and timely. Cellectis is seeing the first dose of pain at the moment and for sure it will see more along the way in developing this exciting but more challenging next generation of CAR-T therapy. But believe me, eventually this new technology will be successfully developed, as these side effects, although life-threatening, are nothing new to hematologists/oncologists and can be managed with appropriate measures and interventions. It is just a matter of time to find the best risk-minimization approach to release its full clinical benefit potential with manageable risks. I don’t know how long it will take but I’m very confident to see it become a reality in just a few years either via CLLS or other biotech companies in exploring this new frontier.