Investors have focused upon the durability of response in patients without first of all considering the durability of the CAR T cells. The study by Rakhshandehroo et al., highlights the point that durable remissions for CAR T cell therapies remain limited. In an article from the University of Basel published in December 2021 titled
T cells: No time to die, we quickly discover that the production of T cells themselves get fewer as we get older and that health depends upon how long our T cells survive.
It has become apparent that the durability of response in CAR T therapies is intrinsically tied to how long the CAR T cells survive in a hostile environment where signalling pathways are critical for both T cell and CAR T cell viability.
And now we come to the emerging data from the azer-cel Phase 1b trial, Cohort B. Imugene have focused upon a signalling pathway that promotes T cell survival: IL-2. We discover from the scientific literature that IL-2 family cytokines play an important role in protecting T cells from apoptosis. The data to date is promising; interesting to investors, interesting to the scientific community and we can only guess, extremely interesting to Pharma with a stake in CAR T therapies.
Rakhshandehroo et al. have worked on a CAR enhancer to increase the activity and persistence of CAR T cells. From their article we read that the CAR enhancer comprises a CAR T cell antigen fused to an immunomodulatory molecule. Imugene have gone with an IL-2 that is available on market and approved for certain kinds of cancers albeit not blood cancer. Its worth reprising the recent comment by
@Outlander2 that
believe it or not, but there has been limited deep research around IL-2 to date because there is seen to be ‘little money in it’.
Autologous CAR-T therapies do not utilise IL-2 in their dosing regimen. Outlander makes the point that IMU have clearly backed themselves. The continuing enrolment into Cohort 2 of the azer-cel phase 1b trial could be absolutely pivotal for the future of cellular therapy.
(20min delay)