Authored by Brian Koffman, MDCM )retired), MSEd
Bottom Line:
CAR-T is an amazing option for CLL. However, its expense and complexity render it inaccessible to many. Making CAR-T cells in the body (in vivo) changes everything.
Where And Who:
At the American Society of Hematology Annual Meeting (ASH 2024) in San Diego, Jacob Garcia, MD, and Ryan Larson, PhD from Umoja Pharmaceutical, presented aspirational goals for a new way to treat chronic lymphocytic leukemia (CLL).
Background:
CAR-T therapy harnesses the patient’s own immune system to fight their CLL, and for some, it is their last best hope. However, the process is extremely complicated and expensive because it is bespoke (individualized) for each patient. It can take weeks, and there are many possible problems in production. For an overview of the whole process, this brochure provides a good background.
What’s Different:
Drs. Jacob and Larson explain that this would be an “off the shelf” treatment, the same for everyone, therefore drastically cutting costs. It simply consists of a vial of frozen viral particles injected once into the bloodstream or a lymph node of the CLL patient. It then uses the best possible factory for CAR-T manufacturing, namely the patient’s own body. It’s been done in monkeys with good results, and the first human in vivo trial is coming soon.
The Potential and the Risk:
This technological advance can potentially democratize CAR-T as the complex manufacturing step is cut out. Yet there is good reason to believe that all the risks would persist for all CAR-T’s known complications seen when the cells expand, including Cytokine Release Syndrome (CRS) and ICANS (neurotoxicity). And we don’t know what we don’t know. How safe it will be? Could the viral DNA be integrated into other cells besides the target T-cells? What could happen then? Genetic engineering is fraught with risks and informed by a history of unexpected dire consequences and lifesaving breakthroughs.
Conclusions:
CAR-T therapy was itself a radical and dangerous “science fiction” therapy not that long ago. Today, it’s a viable, practical, lifesaving option for many cancers, including CLL. It’s even being used to calm down some non-life-threatening but miserable, uncontrolled auto-immune conditions. In vivo CAR-T manufacturing brings a whole new level of promise and risk. We are just at the beginning of the beginning. Only time will tell if this is the next best thing or a dangerous wrong turn.
Links and Resources:
Watch the brief aspirational interview from ASH 2024 and form your opinion.
