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将 HER2 导向的树突状细胞纳入早期 HER2+ER-乳腺癌新辅助治疗的初步研究

英文原题:A pilot study incorporating HER2-directed dendritic cells into neoadjuvant therapy of early stage HER2+ER- breast cancer.

PubMed 2025/03/17(内容时间) NPJ Breast Cancer Q1 · IF 8.4(JCR 2025)

研究概要

HER2-DC1(2×10 7 个细胞/疫苗)在化疗前给予3周,淋巴结内(IN)每周1次(A组)、IN每周2次(B组)、以及每周2次交替瘤内(IT)和IN(C组)。

中文摘要

靶向HER2的1型树突状细胞疫苗(HER2-DC1)可重新激活抗肿瘤免疫,且与新辅助治疗反应相关。一项在新辅助治疗前使用HER2-DC1的初步试验(clinicaltrials.gov,NCT03387553,1/2/2018)评估了可行性/安全性以及病理缓解率和免疫原性。入组了接受新辅助多西他赛/卡铂/曲妥珠单抗/帕妥珠单抗(TCHP)治疗的II-III期ER-HER2+乳腺癌患者。HER2-DC1(2×10 7个细胞/疫苗)在化疗前给予3周,方案为淋巴结内(IN)每周1次(A组)、IN每周2次(B组),以及每周2次交替瘤内(IT)和IN注射(C组)。进行了HER2 ELISPOT计数(EHC)和活检组织的免疫荧光分析。A组和B组共入组6例患者,C组18例患者。新辅助HER2-DC1未显示非预期安全性信号。A、B、C组的病理完全缓解率(pCR)分别为42.8%、66.6%和72.7%。淋巴结内HER2-DC1增加了EHC,但IT + IN HER2-DC1降低了EHC,可能是由于T细胞向肿瘤迁移增加。免疫荧光显示IT + IN注射后T细胞浸润增加。有必要进一步开展IT HER2-DC1研究。

展开英文摘要原文

Type 1 dendritic cell vaccines targeting HER2 (HER2-DC1) reinvigorates antitumor immunity which correlates with neoadjuvant therapy response. A pilot trial (clinicaltrials.gov,NCT03387553,1/2/2018) using HER2-DC1 pre-neoadjuvant therapy evaluated feasibility/safety and pathologic response rates/immunogenicity. Stage II-III ER-HER2+ breast cancer patients prescribed neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) were enrolled. HER2-DC1 (2×10 7 cells/vaccine) was given for 3 weeks prior to chemotherapy intranodal (IN) 1x/week (Arm A), IN 2x/week (Arm B), and 2x/week alternating intratumoral (IT) and IN (Arm C). HER2 ELISPOT counts (EHC) and immunofluorescence analysis of biopsies were performed. Six patients enrolled in Arms A and B, 18 patients in Arm C. Neoadjuvant HER2-DC1 demonstrated no unexpected safety signals. Pathologic complete response rates (pCR) across arms A, B, C were 42.8%, 66.6%, and 72.7%. Intranodal HER2-DC1 increased EHC, but IT + IN HER2-DC1 reduced EHC, possibly due to increased T cell tumor trafficking. Immunofluorescence showed increased T cell infiltration following IT + IN injections. Additional IT HER2-DC1 investigation is warranted.

论文信息

作者
Soliman H、Aldrich A、Abdo N、Han H、Soyano A、Costa R、Armaghani A、Kiluk J
单位
Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. hatem.soliman@moffitt.org.United States
期刊
NPJ breast cancer2025 Mar 17
原文标识
PubMed 40097486 · DOI 10.1038/s41523-025-00742-x