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Multicolor Light-Induced Immune Activation via Polymer Photocaged Cytokines.
Birnbaum, Lacey A; Sullivan, Emily C; Do, Priscilla; Uricoli, Biaggio; Raikar, Sunil S; Porter, Christopher C; Henry, Curtis J; Dreaden, Erik C.
Afiliação
  • Birnbaum LA; Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, United States.
  • Sullivan EC; Molecular and Systems Pharmacology Graduate Program, Emory University School of Medicine, Atlanta, Georgia 30307, United States.
  • Do P; Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, United States.
  • Uricoli B; Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, United States.
  • Raikar SS; Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, United States.
  • Porter CC; Department of Pediatrics, Emory School of Medicine, Atlanta, Georgia 30322, United States.
  • Henry CJ; Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States.
  • Dreaden EC; Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, United States.
Biomacromolecules ; 24(3): 1164-1172, 2023 03 13.
Article em En | MEDLINE | ID: mdl-36745712
ABSTRACT
Cytokines act as potent, extracellular signals of the human immune system and can elicit striking treatment responses in patients with autoimmune disease, tissue damage, and cancer. Yet, despite their therapeutic potential, recombinant cytokine-mediated immune responses remain difficult to control as their administration is often systemic, whereas their intended sites of action are localized. To address the challenge of spatially and temporally constraining cytokine signals, we recently devised a strategy whereby recombinant cytokines are reversibly inactivated via chemical modification with photo-labile polymers that respond to visible LED light. Extending this approach to enable both in vivo and multicolor immune activation, here we describe a strategy whereby cytokines appended with heptamethine cyanine-polyethylene glycol are selectively re-activated ex vivo using tissue-penetrating near-infrared (NIR) light. We show that NIR LED light illumination of caged, pro-inflammatory cytokines restores cognate receptor signaling and potentiates the activity of T cell-engager cancer immunotherapies ex vivo. Using combinations of visible- and NIR-responsive cytokines, we further demonstrate multiwavelength optical control of T cell cytolysis ex vivo, as well as the ability to perform Boolean logic using multicolored light and orthogonally photocaged cytokine pairs as inputs and T cell activity as outputs. Together, this work demonstrates a novel approach to control extracellular immune cell signals using light, a strategy that in the future may improve our understanding of and ability to treat cancer and other diseases.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Citocinas / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Citocinas / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article