一般的ウイルスに対する免疫を膵臓がん治療に活用(Immunity Against Common Virus Leveraged Against Pancreatic Cancer)

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2026-02-09 カリフォルニア大学サンディエゴ校(UCSD)

米カリフォルニア大学サンディエゴ校(UCSD)の研究チームは、一般的なウイルスに対する既存の免疫応答を活用し、膵臓がんに対抗する新たな免疫療法戦略を開発した。研究では、多くの人が免疫記憶を持つ一般的ウイルス由来の抗原を腫瘍内に提示させることで、体内に既に存在するT細胞を再活性化し、がん細胞を標的化させる仕組みを構築した。動物モデルでは腫瘍増殖の有意な抑制が確認され、免疫チェックポイント阻害剤との併用により効果がさらに増強された。従来治療が難しい膵臓がんに対し、既存免疫を再利用するこのアプローチは、個別化がん免疫療法の新たな可能性を示す成果である。

一般的ウイルスに対する免疫を膵臓がん治療に活用(Immunity Against Common Virus Leveraged Against Pancreatic Cancer)This image shows a test tumor from a CMV-infected mouse, treated with CMV peptides. Pink represents cell death. Credit: UC San Diego Health Sciences

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膵臓癌に対するサイトメガロウイルス免疫のリダイレクトによる免疫療法 Redirecting cytomegalovirus immunity against pancreas cancer for immunotherapy

Remi Marrocco,Jay Patel,Rithika Medari,Philip Salu,Eduardo Lucero-Meza,…
Journal for ImmunoTherapy of Cancer  Published:4 February 2026

Abstract

Background Immunotherapy has had limited success in pancreatic cancer, largely due to a low mutational burden and immunosuppressive microenvironment. Here we hypothesized that systemic delivery of viral antigens can redirect pre-existing antiviral immunity against pancreatic tumors.

Methods Cytomegalovirus (CMV, a β-herpesvirus) was chosen, as the majority of the population is infected and it induces an extremely large/broad memory T-cell response. Mice latently infected with murine CMV (MCMV) were orthotopically implanted with pancreatic cancer cells and treated with systemic injections of MCMV T-cell epitopes. Tumor growth was monitored by ultrasound two times a week, and immune cell infiltration was analyzed by histology, flow cytometry and single-cell RNA sequencing (scRNA-seq). Statistical analysis was performed by two-way analysis of variance with Sidak correction.

Results MCMV peptide-epitope therapy (MCMVp) promoted preferential accumulation of MCMV-specific T cells within pancreatic tumors, delaying tumor growth and increasing survival. Immunophenotyping and scRNA-seq analyses showed these T cells were highly activated and cytotoxic, leading to increased tumor necrosis and caspase-3 activation. Depletion of CD4 and CD8 T cells abolished the impact of MCMVp therapy, indicating the antitumor response is T-cell dependent. Together, these results show that CMV-specific T cells can be repurposed to combat pancreatic cancer.

Conclusions Our studies reveal that CMV-specific viral memory T cells can be re-directed to control a solid tumor normally refractory to immunotherapy via a simple, intravenous injection of T-cell peptide epitopes. This mutation-agnostic approach has significant potential for the development of “off-the-shelf” therapeutics by stimulating pre-existing antiviral memory, and it is widely applicable due to the high prevalence of CMV.

細胞遺伝子工学
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