Tumor neoantigens as key drivers of significant anti-tumor immunity in triple-negative breast cancer mouse models

被引：0

作者：

Her, Yujeong ^{[1
]}

Kim, Jeong Yeon ^{[2
,3
]}

Shin, Hocheol ^{[4
,5
]}

Yu, Kwangmin ^{[6
]}

Lee, Kyu-Jin ^{[1
]}

Na, Yi Rang ^{[6
,7
,8
]}

Jon, Sangyong ^{[4
,5
]}

Choi, Jung Kyoon ^{[2
,3
]}

Moon, Hyeong-Gon ^{[9
,10
,11
,12
]}

机构：

[1] Seoul Natl Univ, Coll Med, Interdisciplinary Program Canc Biol, Seoul, South Korea

[2] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Daejeon, South Korea

[3] Penta Medix Co Ltd, Seongnam, South Korea

[4] Korea Adv Inst Sci & Technol KAIST, KAIST Inst BioCentury, Dept Biol Sci, Daejeon, South Korea

[5] Korea Adv Inst Sci & Technol KAIST, Ctr Precis Bionanomed, Daejeon 34141, South Korea

[6] Seoul Natl Univ Hosp, Biomed Res Inst, Immunol Core Facil, Seoul, South Korea

[7] Seoul Natl Univ Hosp, Dept Transdisciplinary Med, Translat Immunol Lab, Seoul 03080, South Korea

[8] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 03080, South Korea

[9] Seoul Natl Univ Hosp, Dept Surg, Seoul, South Korea

[10] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea

[11] Seoul Natl Univ, Genom Med Inst, Med Res Ctr, Seoul, South Korea

[12] Seoul Natl Univ, Canc Res Inst, Seoul, South Korea

来源：

NEOPLASIA | 2025年 / 67卷

关键词：

Neoantigen; Immunotherapy; Triple negative Breast cancer; Tumor immune microenvironment; Checkpoint blockade; Lipid nanoparticle; T cell; DENDRITIC CELLS; T-CELLS; IMMUNOTHERAPY; PEMBROLIZUMAB; ACTIVATION; RESPONSES; ANTIGENS; EFFICACY; VACCINES; PATIENT;

D O I：

10.1016/j.neo.2025.101205

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Recent studies have highlighted the therapeutic potential of targeting tumor neoantigens in solid tumors; however, its efficacy in breast cancer remains unclear. Here, we evaluate the impact of tumor neoantigentargeted strategies in a syngeneic mouse mammary carcinoma model. Mice previously exposed to 4T1 tumor cells (PETCs) or treated with tumor cell-derived lysates (TdLs) exhibited robust antitumor immunity, leading to reduced tumor growth and metastasis through tumor immune microenvironment remodeling. TdL administration in mice harboring orthotopic tumors significantly enhanced the efficacy of immune checkpoint blockade, suggesting its potential as an immunotherapeutic adjuvant. To further optimize neoantigen-based approaches, we developed a lipid nanoparticle (LNP)-based delivery system for neoantigen peptides, which effectively suppressed tumor progression and metastasis in vivo. Mechanistically, this strategy promoted antigen-specific T cell activation and reshaped the tumor immune landscape, enhancing immune-mediated tumor rejection. These findings underscore the therapeutic promise of personalized tumor neoantigen-targeted immunotherapy in breast cancer and support its further evaluation in clinical settings.

引用

页数：19

共 61 条

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