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CAR-T immunotherapy: how will it change treatment for acute lymphoblastic leukemia and beyond?
1Department of Pediatrics and Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Introduction:
The recent approval of CD19 chimeric antigen receptor (CAR) T cells for refractory or second relapse of B cell acute lymphoblastic leukemia (B-ALL) has led to a paradigm shift. Besides being an alternative to chemotherapy and antibody-based approaches, CAR-T cells have become the first successful example of "personalized medicine."
Areas Covered:
In clinical trials, tisagenlecleucel demonstrated higher response rates than prior therapies, and led to durable remissions lasting up to years for some children. Toxicities like cytokine release syndrome and neurotoxicity, while potentially reversible, have limited usage of CAR-T cells at certified centers with expertise in cellular therapy. Strategies to deal with B-ALL relapse after CAR-T remain an open area of research.
Expert Opinion:
Going forward, improvements will likely be seen in managing the side effects of CAR-T therapy as well as usage of CAR-T cells upfront as a replacement for chemotherapy or allogeneic bone marrow transplant for B-ALL. Further advances will need to reduce the biomanufacturing time needed to generate CAR-T cells as well as develop biomarkers that predict CAR-T persistence and/or toxicities.
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Net Change Theorem
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Work Done During Volume Change
Consider a gas confined to a cylinder fitted with a movable piston at one end. If the gas expands from volume V1 to volume V2, it exerts a force on the piston, such that the piston moves by a distance dr.
The work done by the gas on the piston can be expressed as
Le Chatelier's Principle: Changing Temperature
To understand this phenomenon, consider the elementary reaction:

