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Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors.
Grosskopf, Abigail K; Labanieh, Louai; Klysz, Dorota D; Roth, Gillie A; Xu, Peng; Adebowale, Omokolade; Gale, Emily C; Jons, Carolyn K; Klich, John H; Yan, Jerry; Maikawa, Caitlin L; Correa, Santiago; Ou, Ben S; d'Aquino, Andrea I; Cochran, Jennifer R; Chaudhuri, Ovijit; Mackall, Crystal L; Appel, Eric A.
Afiliación
  • Grosskopf AK; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
  • Labanieh L; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Klysz DD; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Roth GA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Xu P; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Adebowale O; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
  • Gale EC; Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
  • Jons CK; Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA.
  • Klich JH; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Yan J; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Maikawa CL; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Correa S; Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA.
  • Ou BS; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • d'Aquino AI; Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA.
  • Cochran JR; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
  • Chaudhuri O; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Mackall CL; Department of Mechanical Engineering, Stanford University, Stanford, CA 94305, USA.
  • Appel EA; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sci Adv ; 8(14): eabn8264, 2022 04 08.
Article en En | MEDLINE | ID: mdl-35394838
ABSTRACT
Adoptive cell therapy (ACT) has proven to be highly effective in treating blood cancers, but traditional approaches to ACT are poorly effective in treating solid tumors observed clinically. Novel delivery methods for therapeutic cells have shown promise for treatment of solid tumors when compared with standard intravenous administration methods, but the few reported approaches leverage biomaterials that are complex to manufacture and have primarily demonstrated applicability following tumor resection or in immune-privileged tissues. Here, we engineer simple-to-implement injectable hydrogels for the controlled co-delivery of CAR-T cells and stimulatory cytokines that improve treatment of solid tumors. The unique architecture of this material simultaneously inhibits passive diffusion of entrapped cytokines and permits active motility of entrapped cells to enable long-term retention, viability, and activation of CAR-T cells. The generation of a transient inflammatory niche following administration affords sustained exposure of CAR-T cells, induces a tumor-reactive CAR-T phenotype, and improves efficacy of treatment.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Receptores Quiméricos de Antígenos / Neoplasias Límite: Humans Idioma: En Revista: Sci Adv Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Receptores Quiméricos de Antígenos / Neoplasias Límite: Humans Idioma: En Revista: Sci Adv Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos