PARTNERS WITH
Tisagenlecleucel // Kymriah
CAR-T ( Chimeric antigen receptor -T cell therapy)
MECHANISM OF ACTION
Mech of action: KYMRIAH is a CD19-directed genetically modified autologous T cell immunotherapy which involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing malignant and normal cells. The CAR is comprised of a murine single-chain antibody fragment which recognizes CD19 and is fused to intracellular signaling domains from 4-1BB (CD137) and CD3 zeta. The CD3 zeta component is critical for initiating T cell activation and antitumor activity, while 4-1BB enhances the expansion and persistence of KYMRIAH. Upon binding to CD19-expressing cells, the CAR transmits a signal to promote T cell expansion, activation, target cell elimination, and persistence of the KYMRIAH cells.
Elimination: unknown
MECHANISM OF KIDNEY INJURY
ATN (Acute tubular necrosis), injury from CRS leading to decreased perfusion.
CLINICAL KIDNEY SYNDROME
AKI, Oliguria, CRS
CARDIOVASCULAR ADVERSE EFFECTS
LYTE ABNORMALITIES
Hypokalemia, Hyponatremia, Hypophosphatemia, Hypomagnesemia, Hypoalbuminemia, Nephrotic range proteinuria - 1 case described.
RISK FACTORS
MITIGATION STRATEGIES
treatment for CRS
SUGGESTIONS
if CRS - tocilizumab and steroids
NOTES/COMMENTS
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PHARMACOKINETICS
Molecular Weight
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Volume of Distribution
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Plasma Protein Binding
Metabolism
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Bioavailability
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Half-life elimination
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Time to peak
Maximal expansion in peripheral blood is 9-13 days after infusion
Excretion
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Dialyzable?
Unknown
REF:
PATHOLOGY SLIDES:
ENTRY UPDATES:
Marco Bonilla
Chicago/USA
Sep 25, 2022