下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:A pilot study incorporating HER2-directed dendritic cells into neoadjuvant therapy of early stage HER2+ER- breast cancer.
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)。
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。
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.
MEMBER ACCOUNT
登录成功会直接打开下一页。