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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

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