ArticleProceedings of the National Academy of Sciences of the United States of America2022
Synergy of a STING agonist and an IL-2 superkine in cancer immunotherapy against MHC I-deficient and MHC I
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- ITPKB is a conserved regulator of natural killer cell desensitization/education that constrains antitumor immunity.bioRxiv : the preprint server for biology · 2026Article
- Intratumoral TScience immunology · 2026Article
- Activation of stimulator of interferon genes (STING) and inhibition of vascular endothelial growth factor receptor (VEGFR) by telatinib induce antitumor activity.The Journal of biological chemistry · 2026Article
- The cGAS-STING pathway and mitochondrial metabolism: from mechanistic insights to therapeutic potential in tumor.Journal of translational medicine · 2026Review
- A monoclonal antibody that inhibits the shedding of CD16a and CD16b and promotes antibody-dependent cellular cytotoxicity against tumors.Nature communications · 2025Article
- Unlocking the therapeutic potential of the STING signaling pathway in anti-tumor treatment.Clinical and experimental medicine · 2025Review
- Improvement of the Anticancer Efficacy of PD-1/PD-L1 Blockade: Advances in Molecular Mechanisms and Therapeutic Strategies.MedComm · 2025Review
- Toll-Like Receptors in the Immunotherapy Era: Dual-Edged Swords of Tumor Immunity and Clinical Translation.MedComm · 2025Review
- Regulation of cGAS-STING signalling and its diversity of cellular outcomes.Nature reviews. Immunology · 2025Review
- STING Agonists and How to Reach Their Full Potential in Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Neoleukin-2/15-armored CAR-NK cells sustain superior therapeutic efficacy in solid tumors via c-Myc/NRF1 activation.Signal transduction and targeted therapy · 2025Article
- Coordinating interleukin-2 encoding circRNA with immunomodulatory lipid nanoparticles to potentiate cancer immunotherapy.Science advances · 2025Article
- Article
- Combination of STING agonist with anti-vascular RGD-(KLAKLAK)Cancer immunology, immunotherapy : CII · 2024Article
- Human NK cells and cancer.Oncoimmunology · 2024Review
- Molecular reshaping of phage-displayed Interleukin-2 at beta chain receptor interface to obtain potent super-agonists with improved developability profiles.Communications biology · 2023Article
- A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity.Nature communications · 2023Article
- Targeting cGAS/STING signaling-mediated myeloid immune cell dysfunction in TIME.Journal of biomedical science · 2023Review
- Cancer nanomedicine in preoperative therapeutics: Nanotechnology-enabled neoadjuvant chemotherapy, radiotherapy, immunotherapy, and phototherapy.Bioactive materials · 2023Review
- NK Cells in Cancer: Mechanisms of Dysfunction and Therapeutic Potential.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Cyclic dinucleotides (CDN) and Toll-like receptor (TLR) ligands mobilize antitumor responses by natural killer (NK) cells and T cells, potentially serving as complementary therapies to immune checkpoint therapy. In the clinic thus far, however, CDN therapy targeting stimulator of interferon genes (STING) protein has yielded mixed results, perhaps because it initiates responses potently but does not provide signals to sustain activation and proliferation of activated cytotoxic lymphocytes. To improve efficacy, we combined CDN with a half life-extended interleukin-2 (IL-2) superkine, H9-MSA (mouse serum albumin). CDN/H9-MSA therapy induced dramatic long-term remissions of the most difficult to treat major histocompatibility complex class I (MHC I)–deficient and MHC I+ tumor transplant models. H9-MSA combined with CpG oligonucleotide also induced potent responses. Mechanistically, tumor elimination required CD8 T cells and not NK cells in the case of MHC I+ tumors and NK cells but not CD8 T cells in the case of MHC-deficient tumors. Furthermore, combination therapy resulted in more prolonged and more intense NK cell activation, cytotoxicity, and expression of cytotoxic effector molecules in comparison with monotherapy. Remarkably, in a primary autochthonous sarcoma model that is refractory to PD-1 checkpoint therapy, the combination of CDN/H9-MSA with checkpoint therapy yielded long-term remissions in the majority of the animals, mediated by T cells and NK cells. This combination therapy has the potential to activate responses in tumors resistant to current therapies and prevent MHC I loss accompanying acquired resistance of tumors to checkpoint therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.