CAR-T Mechanism of Action | KYMRIAH® (tisagenlecleucel)

Mechanism of Action

KYMRIAH MOA Video

Watch this video to learn more about the KYMRIAH^® (tisagenlecleucel) mechanism of action.

About KYMRIAH

KYMRIAH is an individualized therapy that reprograms a patient's own T cells with a chimeric antigen receptor (CAR) containing a 4-1BB costimulatory domain. The 4-1BB costimulatory domain is responsible for enhancing the expansion and persistence of KYMRIAH. The KYMRIAH CAR also contains a CD3ζ intracellular signaling domain, which is critical for initiating T cell activation and antitumor activity.¹

KYMRIAH CAR-T mechanism of action

Costimulatory domains vary by CARs:

4-1BB (KYMRIAH)

CD28

Enhances early expansion and endurance in vivo and in vitro^2,3
Induces central memory T cell differentiation in vitro^3,4:

—Enduring protection

—Immunosurveillance

Improves persistence of the CAR-T cells^1,5

Enhances early and rapid expansion in vivo and in vitro^2,6
Correlated with effector memory T cell differentiation in vitro³:

—Immediate protection

—Limited long-term persistence

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References: 1. Kymriah [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp. 2. Milone MC, Fish JD, Carpenito C, et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther. 2009;17(8):1453-1464. 3. Kawalekar OU, O'Connor RS, Fraietta JA. et al. Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells. Immunity. 2016;44(2):380-390. 4. Kalos M, Levine BL, Porter DL, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011;3(95):95ra73. doi:10.1126/scitranslmed.3002842. 5. Long AH, Haso WM, Shem JF, et al. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat Med. 2015;21(6):581-590. 6. Zhao Z, Condomines M, van der Stegen SJC, et al. Structural design of engineered costimulation determines tumor rejectlon kinetics and persistence of CAR T cells. Cancer Cell. 2015;28(4):415-428.