Tisagenlecleucel
Identification
- Name
- Tisagenlecleucel
- Accession Number
- DB13881
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Cell transplant therapies
Autologous cell transplant - Description
Tisagenlecleucel is a CD19-directed genetically modified autologous T cell immunotherapy, or a CAR-T cell therapy for B-cell acute lymphoblastic leukemia. It was granted approval by FDA in August 2017 under the market name Kymriah. Tisagenlecleucel is an immunocellular therapy that involves autologous T cells that are collected from each individual patient and genetically engineered to express a specific protein called a chimeric antigen receptor (CAR) that specifically target CD19 antigens. Modified T cells are infused back into the patient's body. These CD19-directed chimeric antigen receptors (CD19 CAR-T cells) direct the T cells to targt and kill leukiemia cells that express a specific antigen (CD19) on the cell surface.
In a multicenter clinical trial involving pediatric and young adult patients with relapsed or refractory B-cell precursor ALL, the overall remission rate within three months of treatment was 83 percent 4.
- Synonyms
- Adoptive immunotherapy agent CTL019
- CAR.CD19-Redirected T cells
- Tisagenlecleucel-T
- External IDs
- CART-19 / CART19 / CTL-019 / CTL019
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Unlock Additional DataKymriah Injection, suspension 2000000 1/1 Intravenous Novartis Pharmaceuticals Corporation 2017-08-30 Not applicable US 
Kymriah Suspension 600000000 cells Intravenous Novartis 2019-05-24 Not applicable Canada 
Kymriah Injection, suspension 60000000 1/1 Intravenous Novartis Pharmaceuticals Corporation 2018-05-01 Not applicable US Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
Learn more
- Categories
- UNII
- Q6C9WHR03O
- CAS number
- 1823078-37-0
Pharmacology
- Indication
Indicated for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse Label.
- Associated Conditions
- Pharmacodynamics
Tisagenlecleucel demonstrates efficacy in re-inducing remission in patients with refractory B-cell precursor acute lymphoblastic leukemia. The sole purpose of the therapy is to eliminate CD19-expressing malignant and normal cells with specificity and increased chance of remission.
- Mechanism of action
Tisagenlecleucel is a CD19-directed genetically modified autologous T cell immunotherapy that involves genetically modified autologous T cells isolated from each individual patient. The reprogramming of the patient's T cells uses a lentiviral vector to encode an anti-CD19 chimeric antigen receptor (CAR). The CAR is comprised of a murine single-chain antibody fragment (scFv) specific for CD19, followed by a CD8 hinge and transmembrane region that is fused to the intracellular signaling domains from 4-1BB (CD137) and CD3 zeta Label. These intracellular costimulatory signaling domains increase the expansion, longer-term persistence and potency of CAR T cells 1,3: the CD3 zeta component is critical for initiating T-cell activation and antitumor activity, while 4-1BB enhances the expansion and persistence of tisagenlecleucel {FDA Label, A20379]. Upon binding to CD19-expressing cells, the CAR transmits a signal to promote T-cell expansion, activation, target cell elimination, and persistence of the tisagenlecleucel cells Label.
Target Actions Organism AB-lymphocyte antigen CD19 antibodyHumans - Absorption
In pediatric and young adult relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) patients receiving tisagenlecleucel infusion, the mean peak plasma concentration was approximately 34,700 copies/mcg with a median time of 9.91 days to reach this value (Tmax ) Label.
- Volume of distribution
The drug is found to be distributed in the blood as well as the bone marrow. Blood to bone marrow partitioning suggested that tisagenlecleucel distribution in bone marrow was 44% of that present in blood at Day 28 while at Months 3 and 6 tisagenlecleucel distributed at 67% and 69%, respectively, indicating high distribution to bone marrow Label.
- Protein binding
- Not Available
- Metabolism
- Not Available
- Route of elimination
- Not Available
- Half life
The mean half life was 16.8 days in pediatric and young adult relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) patients Label.
- Clearance
- Not Available
- Toxicity
Genotoxicity assay, carcinogenicitiy assay, and studies assesssing the effect of drug on fertility have not been conducted for tisagenlecleucel. According to in vitro T cell expansion studies involving transduced T cells from healthy donors and patients, there is no evidence of transformation and immortality Label.
- Affected organisms
- Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.
Learn moreStructured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.
Learn moreStructured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.
Learn moreInteractions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
References
- General References
- Tasian SK, Gardner RA: CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Ther Adv Hematol. 2015 Oct;6(5):228-41. doi: 10.1177/2040620715588916. [PubMed:26425336]
- Wei G, Ding L, Wang J, Hu Y, Huang H: Advances of CD19-directed chimeric antigen receptor-modified T cells in refractory/relapsed acute lymphoblastic leukemia. Exp Hematol Oncol. 2017 Apr 14;6:10. doi: 10.1186/s40164-017-0070-9. eCollection 2017. [PubMed:28413717]
- Davila ML, Brentjens RJ: CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Clin Adv Hematol Oncol. 2016 Oct;14(10):802-808. [PubMed:27930631]
- FDA Press Announcements: FDA approval brings first gene therapy to the United States [Link]
- External Links
- PubChem Substance
- 347911451
- Wikipedia
- Tisagenlecleucel
- FDA label
- Download (222 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
Form Route Strength Injection, suspension Intravenous 2000000 1/1 Injection, suspension Intravenous 60000000 1/1 Suspension Intravenous 600000000 cells - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
Taxonomy
- Classification
- Not classified
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Receptor signaling protein activity
- Specific Function
- Assembles with the antigen receptor of B-lymphocytes in order to decrease the threshold for antigen receptor-dependent stimulation.
- Gene Name
- CD19
- Uniprot ID
- P15391
- Uniprot Name
- B-lymphocyte antigen CD19
- Molecular Weight
- 61127.985 Da
Drug created on September 01, 2017 12:43 / Updated on December 02, 2019 10:07