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CD19/BAFF-R dual-targeted CAR T cells for the treatment of mixed antigen-negative variants of acute lymphoblastic leukemia.
Wang, Xiuli; Dong, Zhenyuan; Awuah, Dennis; Chang, Wen-Chung; Cheng, Wesley A; Vyas, Vibhuti; Cha, Soung-Chul; Anderson, Aaron J; Zhang, Tiantian; Wang, Zhe; Szymura, Szymon J; Kuang, Benjamin Z; Clark, Mary C; Aldoss, Ibrahim; Forman, Stephen J; Kwak, Larry W; Qin, Hong.
Afiliação
  • Wang X; Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
  • Dong Z; Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
  • Awuah D; Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
  • Chang WC; Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
  • Cheng WA; Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
  • Vyas V; Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
  • Cha SC; Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
  • Anderson AJ; Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
  • Zhang T; Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
  • Wang Z; Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
  • Szymura SJ; Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
  • Kuang BZ; Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
  • Clark MC; Department of Clinical and Translational Project Development, City of Hope, Duarte, CA, 91010, USA.
  • Aldoss I; Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
  • Forman SJ; Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. sforman@coh.org.
  • Kwak LW; Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. lkwak@coh.org.
  • Qin H; Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
Leukemia ; 36(4): 1015-1024, 2022 04.
Article em En | MEDLINE | ID: mdl-35039637
Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent antitumor effects in B-cell malignancies including acute lymphoblastic leukemia (ALL), but antigen loss remains the major cause of treatment failure. To mitigate antigen escape and potentially improve the durability of remission, we developed a dual-targeting approach using an optimized, bispecific CAR construct that targets both CD19 and BAFF-R. CD19/BAFF-R dual CAR T cells exhibited antigen-specific cytokine release, degranulation, and cytotoxicity against both CD19-/- and BAFF-R-/- variant human ALL cells in vitro. Immunodeficient mice engrafted with mixed CD19-/- and BAFF-R-/- variant ALL cells and treated with a single dose of CD19/BAFF-R dual CAR T cells experienced complete eradication of both CD19-/- and BAFF-R-/- ALL variants, whereas mice treated with monospecific CD19 or BAFF-R CAR T cells succumbed to outgrowths of CD19-/BAFF-R+ or CD19+/BAFF-R- tumors, respectively. Further, CD19/BAFF-R dual CAR T cells showed prolonged in vivo persistence, raising the possibility that these cells may have the potential to promote durable remissions. Together, our data support clinical translation of BAFF-R/CD19 dual CAR T cells to treat ALL.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia-Linfoma Linfoblástico de Células Precursoras / Receptores de Antígenos Quiméricos Limite: Animals / Humans Idioma: En Revista: Leukemia Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia-Linfoma Linfoblástico de Células Precursoras / Receptores de Antígenos Quiméricos Limite: Animals / Humans Idioma: En Revista: Leukemia Ano de publicação: 2022 Tipo de documento: Article