Abstract 944: exoSTING: An engineered exosome therapeutic that selectively delivers STING agonist to the tumor resident antigen-presenting cells resulting in improved tumor antigen-specific adaptive immune response

Jang, Su Chul; Moniz, Raymond J.; Sia, Chang Ling; Harrison, Rane A.; Houde, Damian J.; Ross, Nikki L.; Xu, Ke; Lewis, Nuruddeen D.; Bourdeau, Raymond W.; McCoy, Christine; Zi, Tong; Villiger-Oberbek, Agata; Estes, Scott; Sanchez-Salazar, Jorge; Dooley, Kevin; Dahlberg, William K.; Sathyanarayanan, Sriram; Economides, Kyriakos D.

doi:10.1158/1538-7445.sabcs18-944

Cited by 4 publications

(3 citation statements)

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“…We have also demonstrated the combinatorial potential of both surface display and luminal loading approaches by the co-expression of multiple cargoes fused to PTGFRN or BASP1 in a single producer cell ( Figure S5 F). Combining this protein engineering framework with other strategies for ex vivo loading of small molecules 46 or nucleic acids 47 further broadens the utility and modular approach to designing custom EVs for the targeted delivery of payloads to specific cells.…”

Section: Discussionmentioning

confidence: 99%

A versatile platform for generating engineered extracellular vesicles with defined therapeutic properties

Dooley¹,

McConnell²,

Xu³

et al. 2021

Molecular Therapy

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203

169

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Section: Discussionmentioning

confidence: 99%

A versatile platform for generating engineered extracellular vesicles with defined therapeutic properties

Dooley¹,

McConnell²,

Xu³

et al. 2021

Molecular Therapy

Self Cite

203

169

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“…Intratumoral injection of exoSTING to mice bearing checkpoint refractory melanoma tumor cells results in a more potent tumor-specific immune responses and lower systemic cytokine production levels when compared to free STING administration. Combination treatment using exoSTING with PD1 checkpoint inhibitor has also been shown to further enhance anti-tumor immune responses [103].…”

Section: Novel Sting Agonist Delivery Platformsmentioning

confidence: 99%

STING Agonists as Cancer Therapeutics

Amouzegar

Chelvanambi

Filderman

et al. 2021

Cancers

243

175

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The interrogation of intrinsic and adaptive resistance to cancer immunotherapy has identified lack of antigen presentation and type I interferon signaling as biomarkers of non-T-cell-inflamed tumors and clinical progression. A myriad of pre-clinical studies have implicated the cGAS/stimulator of interferon genes (STING) pathway, a cytosolic DNA-sensing pathway that drives activation of type I interferons and other inflammatory cytokines, in the host immune response against tumors. The STING pathway is also increasingly understood to have other anti-tumor functions such as modulation of the vasculature and augmentation of adaptive immunity via the support of tertiary lymphoid structure development. Many natural and synthetic STING agonists have entered clinical development with the first generation of intra-tumor delivered cyclic dinucleotides demonstrating safety but only modest systemic activity. The development of more potent and selective STING agonists as well as novel delivery systems that would allow for sustained inflammation in the tumor microenvironment could potentially augment response rates to current immunotherapy approaches and overcome acquired resistance. In this review, we will focus on the latest developments in STING-targeted therapies and provide an update on the clinical development and application of STING agonists administered alone, or in combination with immune checkpoint blockade or other approaches.

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“…Recently, efforts have been made towards engineering cells that produce custom therapeutic exosomes with a specific surface protein composition, such as IL-12, to target T-and NK-cells. Alternatively, engineering exosomes with a specific glycoprotein to facilitate a selective cellular tropism, combined with exogenous loading of a potent therapeutic agent, such as a cyclic dinucleotide, to stimulate the STING pathway in mature antigen presenting cells has also been explored as a potential therapeutic mechanism [74][75][76].…”

Section: Evs As Delivery Vehiclesmentioning

confidence: 99%

Extracellular Vesicles in Diagnosis and Treatment of Pancreatic Cancer: Current State and Future Perspectives

Lane

Hoff

Cridebring

et al. 2020

Cancers

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Pancreatic cancer remains one of the deadliest diagnoses a patient can receive. One of the reasons for this lethality is that this malignancy is often detected very late due to a lack of symptoms during the early stages. In addition to the lack of symptoms, we currently do not have a reliable biomarker for screening. Carbohydrate antigen (CA) 19-9 has a sensitivity between 79% and 84% and a specificity of 82–90%, making it unreliable for early detection. Recently, there have been numerous studies on the use of extracellular vesicles (EVs) to detect pancreas cancer. This field has been rapidly expanding, with new methods and biomarkers being introduced regularly. This review provides a systematic update on the commonly used and promising methods used in the detection of EVs, biomarkers associated with EVs for early detection and prognosis, as well as studies looking at using EVs as therapeutics. The review ends with remarks about areas to focus on using EVs going forward.

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Abstract 944: exoSTING: An engineered exosome therapeutic that selectively delivers STING agonist to the tumor resident antigen-presenting cells resulting in improved tumor antigen-specific adaptive immune response

Cited by 4 publications

References 0 publications

A versatile platform for generating engineered extracellular vesicles with defined therapeutic properties

A versatile platform for generating engineered extracellular vesicles with defined therapeutic properties

STING Agonists as Cancer Therapeutics

Extracellular Vesicles in Diagnosis and Treatment of Pancreatic Cancer: Current State and Future Perspectives

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