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CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR) in Naive/Memory T Cells for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma.
Larson, Sarah M; Walthers, Christopher M; Ji, Brenda; Ghafouri, Sanaz N; Naparstek, Jacob; Trent, Jacqueline; Chen, Jia Ming; Roshandell, Mobina; Harris, Caitlin; Khericha, Mobina; Schweppe, Thomas; Berent-Maoz, Beata; Gosliner, Stanley B; Almaktari, Amr; Ceja, Melanie Ayala; Allen-Auerbach, Martin S; Said, Jonathan; Nawaly, Karla; Mead, Monica; de Vos, Sven; Young, Patricia A; Oliai, Caspian; Schiller, Gary J; Timmerman, John M; Ribas, Antoni; Chen, Yvonne Y.
Afiliación
  • Larson SM; Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California.
  • Walthers CM; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Ji B; Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California.
  • Ghafouri SN; Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California.
  • Naparstek J; Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California.
  • Trent J; Parker Institute for Cancer Immunotherapy Center at UCLA, Los Angeles, California.
  • Chen JM; Parker Institute for Cancer Immunotherapy Center at UCLA, Los Angeles, California.
  • Roshandell M; Parker Institute for Cancer Immunotherapy Center at UCLA, Los Angeles, California.
  • Harris C; Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California.
  • Khericha M; Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California.
  • Schweppe T; Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California.
  • Berent-Maoz B; Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California.
  • Gosliner SB; Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California.
  • Almaktari A; Parker Institute for Cancer Immunotherapy Center at UCLA, Los Angeles, California.
  • Ceja MA; Department of Chemical and Biomolecular Engineering, UCLA, Los Angeles, California.
  • Allen-Auerbach MS; Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California.
  • Said J; Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California.
  • Nawaly K; Ahmanson Translational Theranostics Division, David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Mead M; Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, California.
  • de Vos S; Parker Institute for Cancer Immunotherapy Center at UCLA, Los Angeles, California.
  • Young PA; Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California.
  • Oliai C; Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California.
  • Schiller GJ; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, California.
  • Timmerman JM; Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California.
  • Ribas A; Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California.
  • Chen YY; Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California.
Cancer Discov ; 13(3): 580-597, 2023 03 01.
Article en En | MEDLINE | ID: mdl-36416874
ABSTRACT
To address antigen escape and loss of T-cell functionality, we report a phase I clinical trial (NCT04007029) evaluating autologous naive and memory T (TN/MEM) cells engineered to express a bispecific anti-CD19/CD20 chimeric antigen receptor (CAR; CART19/20) for patients with relapsed/refractory non-Hodgkin lymphoma (NHL), with safety as the primary endpoint. Ten patients were treated with 36 × 106 to 165 × 106 CART19/20 cells. No patient experienced neurotoxicity of any grade or over grade 1 cytokine release syndrome. One case of dose-limiting toxicity (persistent cytopenia) was observed. Nine of 10 patients achieved objective response [90% overall response rate (ORR)], with seven achieving complete remission [70% complete responses (CR) rate]. One patient relapsed after 18 months in CR but returned to CR after receiving a second dose of CART19/20 cells. Median progression-free survival was 18 months and median overall survival was not reached with a 17-month median follow-up. In conclusion, CART19/20 TN/MEM cells are safe and effective in patients with relapsed/refractory NHL, with durable responses achieved at low dosage levels.

SIGNIFICANCE:

Autologous CD19/CD20 bispecific CAR-T cell therapy generated from TN/MEM cells for patients with NHL is safe (no neurotoxicity, maximum grade 1 cytokine release syndrome) and demonstrates strong efficacy (90% ORR, 70% CR rate) in a first-in-human, phase I dose-escalation trial. This article is highlighted in the In This Issue feature, p. 517.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Linfoma no Hodgkin / Receptores Quiméricos de Antígenos Límite: Humans Idioma: En Revista: Cancer Discov Año: 2023 Tipo del documento: Article
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Linfoma no Hodgkin / Receptores Quiméricos de Antígenos Límite: Humans Idioma: En Revista: Cancer Discov Año: 2023 Tipo del documento: Article