論文 - 詳細
| RRC ID | 78886 |
|---|---|
| 著者 | Okada H, Takahashi K, Yaku H, Kobiyama K, Iwaisako K, Zhao X, Shiokawa M, Uza N, Kodama Y, Ishii KJ, Seno H. |
| タイトル | In situ vaccination using unique TLR9 ligand K3-SPG induces long-lasting systemic immune response and synergizes with systemic and local immunotherapy. |
| ジャーナル | Sci Rep |
| 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. |
| 巻・号 | 12(1) |
| ページ | 2132 |
| 公開日 | 2022-2-8 |
| DOI | 10.1038/s41598-022-05702-0 |
| PII | 10.1038/s41598-022-05702-0 |
| PMID | 35136110 |
| PMC | PMC8825851 |
| MeSH | Animals Antineoplastic Agents, Immunological* / pharmacology Antineoplastic Agents, Immunological* / therapeutic use Cancer Vaccines* / administration & dosage Carcinoma, Pancreatic Ductal* / therapy Colorectal Neoplasms* / therapy Drug Screening Assays, Antitumor Glucans / pharmacology Glucans / therapeutic use Immunity / drug effects Mice Mice, Inbred BALB C Mice, Inbred C57BL Toll-Like Receptor 9* / agonists |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Colon-26(RCB2657) |