Peringatan Keamanan

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.^L41230

Tisagenlecleucel

DB13881

biotech approved investigational

Deskripsi

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 target and kill leukemia cells that express 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.^L942

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) The mean half life was 16.8 days in pediatric and young adult relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) patients.[L41230]

Volume Distribusi 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.[L41230]

Klirens (Clearance) -

Absorpsi

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).^L41230

Metabolisme

Data metabolisme tidak tersedia.

Rute Eliminasi

Data eliminasi belum tersedia.

Interaksi Obat

38 Data

Darbepoetin alfa	The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Tisagenlecleucel.
Erythropoietin	The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Tisagenlecleucel.
Peginesatide	The risk or severity of Thrombosis can be increased when Peginesatide is combined with Tisagenlecleucel.
Methoxy polyethylene glycol-epoetin beta	The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Tisagenlecleucel.
Lidocaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Lidocaine.
Ropivacaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Ropivacaine.
Bupivacaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Bupivacaine.
Cinchocaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Cinchocaine.
Dyclonine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Dyclonine.
Procaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Procaine.
Prilocaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Prilocaine.
Proparacaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Proparacaine.
Meloxicam	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Meloxicam.
Oxybuprocaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Oxybuprocaine.
Cocaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Cocaine.
Mepivacaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Mepivacaine.
Levobupivacaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Levobupivacaine.
Diphenhydramine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Diphenhydramine.
Benzocaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Benzocaine.
Chloroprocaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Chloroprocaine.
Phenol	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Phenol.
Tetrodotoxin	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Tetrodotoxin.
Benzyl alcohol	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Benzyl alcohol.
Capsaicin	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Capsaicin.
Etidocaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Etidocaine.
Articaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Articaine.
Tetracaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Tetracaine.
Propoxycaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Propoxycaine.
Pramocaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Pramocaine.
Butamben	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Butamben.
Butacaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Butacaine.
Oxetacaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Oxetacaine.
Ethyl chloride	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Ethyl chloride.
Butanilicaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Butanilicaine.
Metabutethamine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Metabutethamine.
Quinisocaine	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Quinisocaine.
Ambroxol	The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Ambroxol.
Etrasimod	The risk or severity of immunosuppression can be increased when Tisagenlecleucel is combined with Etrasimod.

Target Protein

B-lymphocyte antigen CD19 CD19

Referensi & Sumber

Artikel (PubMed)

PMID: 26425336
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.
PMID: 28413717
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.
PMID: 27930631
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.

Link

Contoh Produk & Brand

Produk: 4 • International brands: 0

Produk

Kymriah

Injection, suspension • 2000000 1/1 • Intravenous • US • Approved
Kymriah

Injection, suspension • 60000000 1/1 • Intravenous • US • Approved
Kymriah

- • 300600000 cells • Intravenous • EU • Approved
Kymriah

Suspension • 600000000 cells • Intravenous • Canada • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.