Division of Hematology, Department of Medicine, University of North Carolina, Chapel Hill, NC.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
J Immunol. 2023 Jul 15;211(2):219-228. doi: 10.4049/jimmunol.2300077.
Previous work from our group and others has shown that patients with breast cancer can generate a T cell response against specific human epidermal growth factor 2 (HER2) epitopes. In addition, preclinical work has shown that this T cell response can be augmented by Ag-directed mAb therapy. This study evaluated the activity and safety of a combination of dendritic cell (DC) vaccination given with mAb and cytotoxic therapy. We performed a phase I/II study using autologous DCs pulsed with two different HER2 peptides given with trastuzumab and vinorelbine to a study cohort of patients with HER2-overexpressing and a second with HER2 nonoverexpressing metastatic breast cancer. Seventeen patients with HER2-overexpressing and seven with nonoverexpressing disease were treated. Treatment was well tolerated, with one patient removed from therapy because of toxicity and no deaths. Forty-six percent of patients had stable disease after therapy, with 4% achieving a partial response and no complete responses. Immune responses were generated in the majority of patients but did not correlate with clinical response. However, in one patient, who has survived >14 y since treatment in the trial, a robust immune response was demonstrated, with 25% of her T cells specific to one of the peptides in the vaccine at the peak of her response. These data suggest that autologous DC vaccination when given with anti-HER2-directed mAb therapy and vinorelbine is safe and can induce immune responses, including significant T cell clonal expansion, in a subset of patients.
先前我们团队和其他团队的工作表明，乳腺癌患者可以针对特定的人表皮生长因子 2（HER2）表位产生 T 细胞反应。此外，临床前研究表明，这种 T 细胞反应可以通过 Ag 导向的 mAb 治疗来增强。本研究评估了树突状细胞（DC）疫苗联合 mAb 和细胞毒性治疗的活性和安全性。我们使用两种不同的 HER2 肽脉冲自体 DC 进行了 I/II 期研究，该研究联合曲妥珠单抗和长春瑞滨用于 HER2 过表达的研究队列和第二个 HER2 非过表达转移性乳腺癌患者。对 17 例 HER2 过表达和 7 例非过表达疾病患者进行了治疗。治疗耐受性良好，有 1 例患者因毒性而退出治疗，无死亡病例。治疗后 46%的患者病情稳定，4%的患者部分缓解，无完全缓解。大多数患者产生了免疫反应，但与临床反应无关。然而，在一名患者中，她在试验中接受治疗后已经存活超过 14 年，在她反应的高峰期，她的 25%的 T 细胞对疫苗中的一种肽具有特异性，表现出强烈的免疫反应。这些数据表明，自体 DC 疫苗联合抗 HER2 导向 mAb 治疗和长春瑞滨治疗是安全的，并能在部分患者中诱导免疫反应，包括显著的 T 细胞克隆扩增。
