Durable anticancer immunity from intratumoral administration of IL-23, IL-36γ, and OX40L mRNAs

Hewitt, Susannah L.; Bai, Ailin; Bailey, Dyane; Ichikawa, Kana; Zielinski, John; Karp, Russell; Apte, Ameya; Arnold, Kristen; Zacharek, Sima J.; Iliou, Maria S.; Bhatt, Khushbu; Garnaas, Maija; Musenge, Faith; Davis, Ashley; Khatwani, Nikhil; Su, Stephen V.; MacLean, Graham; Farlow, Samuel J.; Burke, Kristine; Frederick, Joshua P.

doi:10.1126/scitranslmed.aat9143

Cited by 317Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

Durable anticancer immunity from intratumoral administration of IL-23, IL-36γ, and OX40L mRNAs

Hewitt, Susannah L., Bai, Ailin, Bailey, Dyane, Ichikawa, Kana, Zielinski, John, Karp, Russell, Apte, Ameya, Arnold, Kristen +12 more·2019·Science Translational Medicine

DOI 10.1126/scitranslmed.aat9143

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Abstract

Local mRNA therapy encoding inflammatory cytokines and T cell costimulator OX40L mediates persistent anticancer immunity across tumor models.

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A pro-inflammatory tumour microenvironment can be induced by lipid nanoparticle-mRNA formulations delivering cytokines or co-stimulatory molecules.
“Alternatively to vaccination, a pro-inflammatory tumour microenvironment can be induced by lipid nanoparticle–mRNA formulations delivering cytokines or co-stimulatory molecules33,106,161,163,214 (Table 2).”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [163]
mRNA-2752, a lipid nanoparticle formulated with mRNA encoding human OX40L, IL-23 and IL-36γ, entered clinical evaluation.
“Encouraged by these results, mRNA-2752, a lipid nanoparticle formulated with mRNA encoding human OX40L, IL-23 and IL-36γ, entered clinical evaluation (NCT03739931)163,215,216.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [163]
Moderna Therapeutics published an anti-cancer immunotherapy using direct intratumoral and LNP-mediated delivery of a mixture of mRNA encoding IL-23, IL-36γ, and OX40(L) ligand.
“In line with this, Moderna Therapeutics recently published on an anti-cancer immunotherapy, using direct intratumoral-and LNP-mediated delivery of a mixture of mRNA encoding IL-23, IL-36γ, and OX40(L) ligand [203].”
From Three decades of messenger RNA vaccine development (2019) · cites this paper as [203]
By localized expression of these immunomodulatory molecules, this strategy was able to break DC tolerance and activate tumor-specific T cell responses.
“By the localized expression of these immunomodulatory molecules, this strategy was able to break DC tolerance and to activate tumor-specific T cell responses.”
From Three decades of messenger RNA vaccine development (2019) · cites this paper as [203]

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Abstract 1607: Durable efficacy and anti-cancer immunity following intratumoral administration of messenger RNAs encoding IL-36γ, IL-23 and OX40L
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Self-citation
Abstract 1711: Induction of anti-tumor immunity by intratumoral delivery of mRNA encoding cytokines and TNFRSF agonists
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Immune checkpoint blockade combined with IL ‐6 and TGF ‐β inhibition improves the therapeutic outcome of m RNA ‐based immunotherapy
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Abstract CT210: A Phase I, open-label, multicenter, dose escalation study of mRNA-2752, a lipid nanoparticle encapsulating mRNAs encoding human OX40L, IL-23, and IL-36γ, for intratumoral injection alone and in combination with immune checkpoint blockade
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Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells
Lint, S. V., Renmans, D., Broos, K., Goethals, L., Maenhout, S. K., Benteyn, D., Goyvaerts, C., Four, S. D., der Jeught, K. V., Bialkowski, L., et al. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0163 · Cited by 130 · see citing works

Authors: Hewitt, S. L., Bai, A., Bailey, D., Ichikawa, K., Zielinski, J., Karp, R., Apte, A., Arnold, K., Zacharek, S. J., Iliou, M. S., Bhatt, K., Garnaas, M., Musenge, F., Davis, A., Khatwani, N., Su, S. V., MacLean, G., Farlow, S. J., Burke, K., & Frederick, J. P.
Affiliations: Moderna Inc., 200 Technology Square, Cambridge, MA 02139, USA.
Corresponding author: Hewitt, Susannah L.
Bai, Ailin
Frederick, Joshua P.
ORCID: Hewitt, Susannah L.
Bai, Ailin
Bailey, Dyane
Ichikawa, Kana
Zielinski, John
Karp, Russell
Apte, Ameya
Arnold, Kristen
Zacharek, Sima J.
Iliou, Maria S.
Bhatt, Khushbu
Garnaas, Maija
Musenge, Faith
Davis, Ashley
Khatwani, Nikhil
Su, Stephen V.
MacLean, Graham
Farlow, Samuel J.
Burke, Kristine
Frederick, Joshua P.
Venue: Science Translational Medicine
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2019-01-30
Volume: 11
Issue: 477
ISSN: 1946-6234 (ISSN-L)
1946-6242
DOI: 10.1126/scitranslmed.aat9143
OpenAlex: W2912510115
Cited by: 316
References: 55
Citations by year: 2026: 41 · 2025: 54 · 2024: 51 · 2023: 57 · 2022: 39 · 2021: 41 · 2020: 26 · 2019: 6 · 2014: 1
FWCI: 11.70
Type: journal article
Language: en
Open access: closed
Locations: Science Translational Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: Moderna Therapeutics
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: IL-23, IL-36γ, OX40L, cancer immunotherapy, tumor-infiltrating T cells, immune checkpoint inhibitor resistance, tumor microenvironment
MeSH terms: Animals, Disease Models, Animal, Humans, Immunity, Inflammation, Interleukin-1, Lymph Nodes, Lymphocyte Activation, Neoplasms, RNA, Messenger, Tissue Distribution, Cell Proliferation, Mice, OX40 Ligand, Interleukin-23, Tumor Microenvironment

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Durable anticancer immunity from intratumoral administration of IL-23, IL-36γ, and OX40L mRNAs

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