767 Safety and preliminary efficacy of mRNA-2752, a lipid nanoparticle encapsulating mRNAs encoding human OX40L/IL-23/IL-36γ for intratumoral (ITu) injection, and durvalumab (IV) in TNBC, HNSCC, and melanoma

Olson, Daniel J.; Daud, Adil; Shapira-Frommer, Ronnie; Jimeno, Antonio; Reagan, Patrick M.; Kummar, Shivaani; Abdul-Karim, Raghad; Stemmer, Salomon M.; McKean, Meredith; Perets, Ruth; Patel, Manish R.; Marron, Thomas U.; Gupta, Shilpa; Desai, Anupam M.; Weber, Jeffrey S.; Margolin, Kim; Park, Jong Chul; Zacharek, Sima J.; Laino, Andressa S.; Frederick, Joshua P.; Milberg, Oleg; Zhu, Lili; Mody, Kinjal; López, Natalia Vila; Aanur, Praveen; Meehan, Robert; Johansen, Lisa M.; Lavoie, Sara; Do, Khanh; Sullivan, Ryan J.; Sweis, Randy F.

doi:10.1136/jitc-2022-sitc2022.0767

Cited by 2 publications

(3 citation statements)

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“…Analyses of plasma and tumour tissues show that mRNA-2752 treatment was associated with elevated pro-inflammatory cytokines, including IL-23, IL-36γ, IFNγ and TNF, and an increase in proliferating CD8 + T cells, dendritic cell recruitment and T cell activation compared to baseline. Increases in immune response positively correlated with clinical benefit 70 .…”

Section: Nbts For Protein Upregulationmentioning

confidence: 98%

Amplifying gene expression with RNA-targeted therapeutics

Khorkova

Stahl

Joji

et al. 2023

Nat Rev Drug Discov

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Many diseases are caused by insufficient expression of mutated genes and would benefit from increased expression of the corresponding protein. However, in drug development, it has been historically easier to develop drugs with inhibitory or antagonistic effects. Protein replacement and gene therapy can achieve the goal of increased protein expression but have limitations. Recent discoveries of the extensive regulatory networks formed by non-coding RNAs offer alternative targets and strategies to amplify the production of a specific protein. In addition to RNA-targeting small molecules, new nucleic acid-based therapeutic modalities that allow highly specific modulation of RNA-based regulatory networks are being developed. Such approaches can directly target the stability of mRNAs or modulate non-coding RNA-mediated regulation of transcription and translation. This Review highlights emerging RNA-targeted therapeutics for gene activation, focusing on opportunities and challenges for translation to the clinic.

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Section: Nbts For Protein Upregulationmentioning

confidence: 98%

Amplifying gene expression with RNA-targeted therapeutics

Khorkova

Stahl

Joji

et al. 2023

Nat Rev Drug Discov

View full text Add to dashboard Cite

show abstract

“…Moreover, mRNA-2752, an LNP encapsulating mRNA encoding OX40L, IL-23, and IL-36𝛾, has been investigated in a phase I study (NCT03739931) as a combination therapy with duralumin against triple negative breast cancer (TNBC), head and neck squamous cell carcinomas (HNSCC) and melanoma. [116,117] Besides using combination of multiple cytokines, altering the kinetics of the protein expression could also be advantageous for improving the efficacy. For example, a study has constructed a saRNA encoding a fusion protein consisting of IL-12, albumin and collagen-binding protein lumican (IL-12-alb-lumican).…”

Section: Mrna Delivery Systems For Local Administrationmentioning

confidence: 99%

“…Moreover, mRNA‐2752, an LNP encapsulating mRNA encoding OX40L, IL‐23, and IL‐36γ, has been investigated in a phase I study (NCT03739931) as a combination therapy with duralumin against triple negative breast cancer (TNBC), head and neck squamous cell carcinomas (HNSCC) and melanoma. [ 116,117 ]…”

Section: Gene Delivery Systemsmentioning

confidence: 99%

Revitalizing Cytokine‐Based Cancer Immunotherapy through Advanced Delivery Systems

Chen

Paraiso²,

Cabral

2023

Macromolecular Bioscience

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Cytokines can coordinate robust immune responses, holding great promise as therapeutics against infections, autoimmune diseases and cancers. In cancer treatment, numerous pro‐inflammatory cytokines have displayed promising efficacy in preclinical studies. However, their clinical application has been hindered by poor pharmacokinetics, significant toxicity and unsatisfactory anticancer efficacy. Thus, while IFN‐α and IL‐2 have been approved for specific cancer treatments, other cytokines still remain subject of intense investigation. To accelerate the application of cytokines as cancer immunotherapeutics, strategies need to be directed to improve their safety and anticancer performance. In this regard, delivery systems could be used to generate innovative therapies by targeting the cytokines or nucleic acids, such as DNA and mRNA, encoding the cytokines to tumor tissues. This review centers on these innovative delivery strategies for cytokines, summarizing key approaches, such as gene delivery and protein delivery, and critically examining their potential and challenges for clinical translation.This article is protected by copyright. All rights reserved

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767 Safety and preliminary efficacy of mRNA-2752, a lipid nanoparticle encapsulating mRNAs encoding human OX40L/IL-23/IL-36γ for intratumoral (ITu) injection, and durvalumab (IV) in TNBC, HNSCC, and melanoma

Cited by 2 publications

References 0 publications

Amplifying gene expression with RNA-targeted therapeutics

Amplifying gene expression with RNA-targeted therapeutics

Revitalizing Cytokine‐Based Cancer Immunotherapy through Advanced Delivery Systems

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