Soliman Hatem, Aldrich Amy, Abdo Neveen, Han Hyo, Soyano Aixa, Costa Ricardo, Armaghani Avan, Kiluk John, Khakpour Nazanin, Lee Marie Catherine, Hoover Susan, Laronga Christine, Niell Bethany, Mooney Blaise, Weinfurtner Robert Jared, Rosa Marilin, Czerniecki Brian
Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
NPJ Breast Cancer. 2025 Mar 17;11(1):29. doi: 10.1038/s41523-025-00742-x.
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 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.
靶向人表皮生长因子受体2（HER2）的1型树突状细胞疫苗（HER2-DC1）可恢复抗肿瘤免疫力，这与新辅助治疗反应相关。一项使用HER2-DC1进行新辅助治疗的试点试验（clinicaltrials.gov，NCT03387553，2018年1月2日）评估了其可行性/安全性以及病理反应率/免疫原性。招募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期雌激素受体阴性（ER-）HER2阳性乳腺癌患者。在化疗前3周，每周1次经淋巴结内（IN）注射给予HER2-DC1（2×10个细胞/疫苗）（A组），每周2次经淋巴结内注射（B组），以及每周2次交替进行瘤内（IT）和经淋巴结内注射（C组）。进行了HER2酶联免疫斑点计数（EHC）和活检的免疫荧光分析。A组和B组有6名患者入组，C组有18名患者入组。新辅助HER2-DC1未显示出意外的安全信号。A、B、C组的病理完全缓解率（pCR）分别为42.8%、66.6%和72.7%。经淋巴结内注射HER2-DC1可增加EHC，但瘤内+经淋巴结内注射HER2-DC1会降低EHC，这可能是由于T细胞向肿瘤的迁移增加所致。免疫荧光显示瘤内+经淋巴结内注射后T细胞浸润增加。有必要对瘤内注射HER2-DC1进行进一步研究。
