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Clinical data
Trade namesKymriah
Routes of
Intravenous infusion
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Elimination half-life16.8 days

Tisagenlecleucel, marketed as Kymriah, is a treatment for B-cell acute lymphoblastic leukemia (ALL) which uses the body's own T cells to fight cancer (adoptive cell transfer).

T cells from a person with cancer are removed, genetically engineered to make a specific chimeric cell surface receptor with components from both a T-cell receptor and an antibody specific to a protein on the cancer cell, and transferred back to the person. The T cells are engineered to target a protein called CD19 that is common on B cells. A chimeric T cell receptor ("CAR-T") is expressed on the surface of the T cell.

It was invented and initially developed at the University of Pennsylvania; Novartis completed development, obtained FDA approval, and markets the treatment.[1] In August 2017, it became the first FDA-approved treatment that included a gene therapy step in the United States.[2]

It is administered in a single treatment, which will cost US$475,000. Novartis says this is cheaper than some bone marrow transplants, and that it will not charge people whose conditions do not respond to the treatment.[3]


The treatment was developed by a group headed by Carl H. June at the University of Pennsylvania, and is licensed to Novartis.[4]

In April 2017, CTL019 received breakthrough therapy designation by the US FDA for the treatment of relapsed or refractory diffuse large B-cell lymphoma.[5]

In July 2017, an FDA advisory committee unanimously recommended that the agency approve it to treat B cell acute lymphoblastic leukemia people who did not respond adequately to other treatments or have relapsed.[6][7][8]

In August 2017 the FDA granted approval for the use of tisagenlecleucel in people with acute lymphoblastic leukemia.[9] According to Novartis, the treatment will be administered at specific medical centers where staff have been trained to manage possible reactions to this new type of treatment.[10]

In May 2018, the FDA further approved tisagenlecleucel to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), based on results from the JULIET phase II trial. [11]

In England, the NHS will use the drug to treat children with ALL if earlier treatments including stem cell transplants have failed; it is expected to apply to between 15 and 20 children.[12] The drug has been licenced to treat adults with diffuse large B-cell lymphoma (DLBCL), but as of September 2018 it had not been decided whether the NHS would use it.[citation needed]

It has undergone a phase 2 clinical study for relapsing/remitting B cell acute lymphoblastic leukemia.[13] A frequent side effect seen is cytokine release syndrome (CRS).[1][7]


In a 22-day process, the treatment is customized for each person. T cells are purified from blood drawn from the person, and those cells are then modified by a virus that inserts a gene into the cells' genome. The gene encodes a chimaeric antigen receptor (CAR) that targets leukaemia cells.[6]

It uses the 4-1BB co-stimulatory domain in its CAR to improve response.[14]


  1. ^ a b "BLA 125646 Tisagenlecleucel - Novartis Briefing document to FDA ODAC" (PDF).
  2. ^ "FDA approval brings first gene therapy to the United States". FDA - U.S. Food & Drug Administration. U.S. Department of Health and Human Services. Retrieved 31 August 2017.
  3. ^ F.D.A. Approves First Gene-Altering Leukemia Treatment, Costing $475,000, By DENISE GRADY, New York Times, AUG. 30, 2017
  4. ^ F.D.A. Panel Recommends Approval for Gene-Altering Leukemia Treatment, By DENISE GRADY, New York Times, JULY 12, 2017
  5. ^ "Novartis gets second CAR-T candidate FDA 'breakthrough' tag". www.fiercebiotech.com. Fierce Biotech.
  6. ^ a b Ledford, Heidi (12 July 2017). "Engineered cell therapy for cancer gets thumbs up from FDA advisers". Nature. doi:10.1038/nature.2017.22304.
  7. ^ a b "FDA Panel Backs Novartis' Pioneering New Cancer Gene Therapy". New York Times. 12 July 2017 – via NYTimes.com.
  8. ^ Stein, Rob (2017-07-12). "'Living Drug' That Fights Cancer By Harnessing The Immune System Clears Key Hurdle". NPR. Retrieved 2017-07-13.
  9. ^ "FDA approval brings first gene therapy to the United States". FDA - Food & Drug Administration. Retrieved 6 September 2017.
  10. ^ Grady, Denise. "F.D.A. Approves First Gene-Altering Leukemia Treatment, Costing $475,000". The New York Times. Retrieved 6 September 2017.
  11. ^ http://www.ascopost.com/issues/may-25-2018/fda-expands-tisagenlecleucel-approval/
  12. ^ Sarah Boseley (5 September 2018). "NHS to treat young cancer patients with expensive 'game changer' drug". The Guardian. Retrieved 5 September 2018.
  13. ^ "Determine Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell ALL". clinicaltrials.gov.
  14. ^ "FDA Panel Unanimously Recommends Approval for Novartis' CAR T-Cell Therapy CTL019". GEN. GEN Genetic Engineering & Biotechnology News.

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