Optical Control of Cytokine Signaling via Bioinspired, Polymer-Induced Latency

Perdue, Lacey A; Do, Priscilla; David, Camille; Chyong, Andrew; Kellner, Anna; Ruggieri, Amanda N.; Kim, Hye Ryong; Salaita, Khalid; Lesinski, Gregory B.; Porter, Christopher C.; Dreaden, Erik C.

doi:10.1021/acs.biomac.0c00264

Cited by 7 publications

(23 citation statements)

References 84 publications

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“…IL-2, IL-12, IL-15) can be blunted via conjugation with a photolabile polyethylene glycol (PEG) and recovered via brief, in this case blue, LED light exposure. 18 While these studies demonstrated the feasibility of in vivo cytokine photoactivation using tissue phantoms, we concluded that the clinical applications of this approach were limited to cutaneous or subdermal tissues and those accessible by in situ light sources (e.g. catheter-guided fiber lasers) as a result of efficient absorption and scattering of light by tissues and biological fluids at visible wavelengths.…”

Section: Introductionmentioning

confidence: 91%

“…Leveraging the ability of NIR photons to efficiently penetrate human tissues, here we advance our prior approach 18 to reversibly photocage immunostimulatory cytokines by using photo-labile PEG that de-shields in response to NIR rather than visible light. We show that LED light exposure of NIR-photocaged cytokines can be used to reversibly modulate cognate cytokine receptor signaling and enhance the activity of bispecific cancer immunotherapies that rely on T celldependent cytolysis.…”

Section: Introductionmentioning

confidence: 99%

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Multicolor Light-Induced Immune Activation via Polymer Photocaged Cytokines

Birnbaum

Sullivan

et al. 2022

Preprint

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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 multi-wavelength 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.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Multicolor Light-Induced Immune Activation via Polymer Photocaged Cytokines

Birnbaum

Sullivan

et al. 2022

Preprint

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Section: Immunostimulatory Cytokinesmentioning

confidence: 99%

“…Inspired by the ability of a subset of cytokines (e.g., TGF‐ β 1, IL‐1 α , IL‐33) to activate in response to various biological stimuli, [ 28 ] we recently hypothesized that modification of cytokines with photolabile polymers could blunt cytokine activity when conjugated, then restore protein function upon exposure to light, allowing for enhanced control over the location, strength, and timescale of cytokine signals (i.e., “photokines,” Figure 1b, Figure ). [ 29 ] We modified IL‐2, IL‐15, and IL‐12 with PEG (5–20 kDa) appended to various o ‐nitrobenzyl linkers and found that simple blue LED light exposure could selectively restore protein activity upon light exposure. Photolabile polymer modification, alone, favorably biased IL‐2 binding toward IL‐2R βγ c , much like NKTR‐214, and improved IL‐12 plasma half‐life 16‐fold following intravenous injection in C57BL/6 mice.…”

Section: Immunostimulatory Cytokinesmentioning

confidence: 99%

Engineered Cytokines for Cancer and Autoimmune Disease Immunotherapy

Uricoli

Birnbaum

et al. 2021

Adv Healthcare Materials

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Cytokine signaling is critical to a range of biological processes including cell development, tissue repair, aging, and immunity. In addition to acting as key signal mediators of the immune system, cytokines can also serve as potent immunotherapies with more than 20 recombinant products currently Food and Drug Administration (FDA)‐approved to treat conditions including hepatitis, multiple sclerosis, arthritis, and various cancers. Yet despite their biological importance and clinical utility, cytokine immunotherapies suffer from intrinsic challenges that limit their therapeutic potential including poor circulation, systemic toxicity, and low tissue‐ or cell‐specificity. In the past decade in particular, methods have been devised to engineer cytokines in order to overcome such challenges and here, the myriad strategies are reviewed that may be employed in order to improve the therapeutic potential of cytokine and chemokine immunotherapies with applications in cancer and autoimmune disease therapy, as well as tissue engineering and regenerative medicine. For clarity, these strategies are collected and presented as they vary across size scales, ranging from single amino acid substitutions, to larger protein‐polymer conjugates, nano/micrometer‐scale particles, and macroscale implants. Together, this work aims to provide readers with a timely view of the field of cytokine engineering with an emphasis on early‐stage therapeutic approaches.

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“…SMANCS neocarzinostatin chemotherapy and Movanik naloxone laxative) and 3) nucleic acids (e.g. Macugen anti-VEGF aptamer antiangiogenic) ( Perdue et al, 2020 ). More recently, polymer conjugation has demonstrated further clinical utility in stabilizing lipid nanoparticles used to deliver small interfering RNA (siRNA, Onpattro) for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis ( Zhang et al, 2020 ), as well as both current mRNA-based vaccines for SARS-CoV-2 (COVID-19), BNT162b2/Comirnaty and mRNA-1273/Spikevax ( Schoenmaker et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%