Afamitresgene autoleucel

DB18592

biotech approved investigational

Deskripsi

Afamitresgene autoleucel is a melanoma-associated antigen A4 (MAGE-A4)-directed genetically modified autologous T cell immunotherapy product consisting of CD4 and CD8 positive T cells transduced with a self-inactivating lentiviral vector (LV) expressing an affinity-enhanced T cell receptor (TCR) specific for the human MAGE-A4.^L51114 MAGE-A4 is an intracellular cancer-testis antigen that is overexpressed by cancer cells in synovial sarcoma.L51114, L51119 Afamitresgene autoleucel is first prepared from the patient’s peripheral blood mononuclear cells (PBMCs), which are enriched for T cells and are then transduced with a replication-incompetent LV containing the MAGE-A4 TCR transgene.^L51114 The transduced T cells are expanded, washed, formulated into a suspension, and cryopreserved.^L51114

On August 2, 2024, the FDA granted the accelerated approval of afamitresgene autoleucel, making it the first FDA-approved TCR gene therapy and the first gene therapy for the treatment of synovial sarcoma.^L51119

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) -

Volume Distribusi -

Klirens (Clearance) -

Absorpsi

Afamitresgene autoleucel exhibited an initial engraftment and expansion phase followed by contraction, and then persistence. High inter-individual variability was observed.^L51114 In patients with synovial sarcoma who received a dose within the range of 2.68 x 109 to 10 x 109 MAGE-A4 TCR positive T cells, the median (range) T_max is 7 (1-89) days. The geometric mean (CV%) C_max is 189269 (109.1%) DNA copies/?g.^L51114

Metabolisme

Data metabolisme tidak tersedia.

Rute Eliminasi

Data eliminasi belum tersedia.

Interaksi Obat

0 Data

Tidak ada data.

Referensi & Sumber

Artikel (PubMed)

PMID: 36624315
Hong DS, Van Tine BA, Biswas S, McAlpine C, Johnson ML, Olszanski AJ, Clarke JM, Araujo D, Blumenschein GR Jr, Kebriaei P, Lin Q, Tipping AJ, Sanderson JP, Wang R, Trivedi T, Annareddy T, Bai J, Rafail S, Sun A, Fernandes L, Navenot JM, Bushman FD, Everett JK, Karadeniz D, Broad R, Isabelle M, Naidoo R, Bath N, Betts G, Wolchinsky Z, Batrakou DG, Van Winkle E, Elefant E, Ghobadi A, Cashen A, Grand'Maison A, McCarthy P, Fracasso PM, Norry E, Williams D, Druta M, Liebner DA, Odunsi K, Butler MO: Autologous T cell therapy for MAGE-A4(+) solid cancers in HLA-A*02(+) patients: a phase 1 trial. Nat Med. 2023 Jan;29(1):104-114. doi: 10.1038/s41591-022-02128-z. Epub 2023 Jan 9.
PMID: 36761952
Fuchs JR, Schulte BC, Fuchs JW, Agulnik M: Emerging targeted and cellular therapies in the treatment of advanced and metastatic synovial sarcoma. Front Oncol. 2023 Jan 25;13:1123464. doi: 10.3389/fonc.2023.1123464. eCollection 2023.
PMID: 16151806
Ottaviani S, Colau D, van der Bruggen P, van der Bruggen P: A new MAGE-4 antigenic peptide recognized by cytolytic T lymphocytes on HLA-A24 carcinoma cells. Cancer Immunol Immunother. 2006 Jul;55(7):867-72. doi: 10.1007/s00262-005-0053-2. Epub 2005 Sep 3.

Link

Contoh Produk & Brand

Produk: 1 • International brands: 0

Produk

Tecelra

Injection, suspension • 10000000000 1/1 • Intravenous • US • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.