ArticleScientific reports2022
In situ vaccination using unique TLR9 ligand K3-SPG induces long-lasting systemic immune response and synergizes with systemic and local immunotherapy.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Long-term immunoprophylaxis by TLR9 ligand mediates macrophage-ILC cross-talk against respiratory viral infection.Science advances · 2026Article
- Review
- Nanomaterials in the diagnosis and treatment of gastrointestinal tumors: New clinical choices and treatment strategies.Materials today. Bio · 2025Review
- In Situ Cancer Vaccines: Redefining Immune Activation in the Tumor Microenvironment.ACS biomaterials science & engineering · 2025Review
- Advances in cancer nanovaccines: a focus on colorectal cancer.Nanomedicine (London, England) · 2025Review
- MR molecular imaging for monitoring and predicting tumor responses to immunotherapy.Theranostics · 2025Article
- Advances in therapeutic cancer vaccines: Harnessing immune adjuvants for enhanced efficacy and future perspectives.Computational and structural biotechnology journal · 2024Review
- Current and future immunotherapeutic approaches in pancreatic cancer treatment.Journal of hematology & oncology · 2024Review
- Toll-like receptors in health and disease.MedComm · 2024Review
- Article
- Toll-Like Receptors and the Response to Radiotherapy in Solid Tumors: Challenges and Opportunities.Vaccines · 2023Review
- In situ vaccination with cowpea mosaic virus elicits systemic antitumor immunity and potentiates immune checkpoint blockade.Journal for immunotherapy of cancer · 2022Article
- Inhibition of IL-12 heterodimers impairs TLR9-mediated prevention of early mouse plasmacytoma cell growth.Frontiers in medicine · 2022Article
- Colorectal cancer vaccines: The current scenario and future prospects.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although checkpoint inhibitors (CPIs) have changed the paradigm of cancer therapy, low response rates and serious systemic adverse events remain challenging. In situ vaccine (ISV), intratumoral injection of immunomodulators that stimulate innate immunity at the tumor site, allows for the development of vaccines in patients themselves. K3-SPG, a second-generation nanoparticulate Toll-like receptor 9 (TLR9) ligand consisting of K-type CpG oligodeoxynucleotide (ODN) wrapped with SPG (schizophyllan), integrates the best of conventional CpG ODNs, making it an ideal cancer immunotherapy adjuvant. Focusing on clinical feasibility for pancreaticobiliary and gastrointestinal cancers, we investigated the antitumor activity of K3-SPG-ISV in preclinical models of pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC). K3-SPG-ISV suppressed tumor growth more potently than K3-ISV or K3-SPG intravenous injections, prolonged survival, and enhanced the antitumor effect of CPIs. Notably, in PDAC model, K3-SPG-ISV alone induced systemic antitumor effect and immunological memory. ISV combination of K3-SPG and agonistic CD40 antibody further enhanced the antitumor effect. Our results imply that K3-SPG-based ISV can be applied as monotherapy or combined with CPIs to improve their response rate or, conversely, with CPI-free local immunotherapy to avoid CPI-related adverse events. In either strategy, the potency of K3-SPG-based ISV would provide the rationale for its clinical application to puncturable pancreaticobiliary and gastrointestinal malignancies.
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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.