帕博利珠单抗联合二甲双胍治疗转移性头颈部癌的 II 期可行性研究
A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.
二甲双胍联合帕博利珠单抗耐受性良好,仅出现轻度胃肠道不良事件,并展现出有前景的活性,值得在随机试验中进一步研究。
英文原题:Apatinib potentiates the therapeutic effect of anti-PD-1 in locally advanced head and neck cancers.
Apatinib potentiates the therapeutic effect of anti-PD-1 in locally advanced head and neck cancers.
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我们的研究表明,阿帕替尼治疗在临床前癌症模型和晚期 HNSCC 患者中与抗 PD-1 抗体产生协同作用。这些结果为在 HNSCC 大规模临床试验中推进这种新辅助免疫治疗提供了新的依据。
抗血管生成抑制剂已被证明能与免疫检查点阻断产生协同作用,但这种协同反应的内在机制尚未完全明了。
我们研究了VEGFR2抑制对体内肿瘤浸润免疫细胞的影响,以及阿帕替尼与抗PD-1联合在HNSCC协同小鼠模型中的活性。一名左舌鳞状细胞癌伴颈部淋巴结转移的患者接受了卡瑞利珠单抗和阿帕替尼的联合诱导治疗,以验证新辅助免疫治疗在手术前的疗效。
我们发现阿帕替尼在临床前同基因小鼠模型中增加了CD8+ T细胞的浸润并减少了Tregs的数量。在阿帕替尼治疗的肿瘤中,CD8+PD1+ T细胞的比例显著增加。阿帕替尼与抗PD-1的联合治疗显示出比单独治疗更好的治疗效果。左舌鳞状细胞癌伴颈部淋巴结的患者在两个周期的联合诱导治疗后达到了主要病理缓解(MPR)。
Antiangiogenic inhibitors have been shown to synergize with immune checkpoint blockade, but the underlying mechanisms of the synergistic response are not fully understood.
We investigate the impact of VEGFR2 inhibition on tumor-infiltrating immune cells in vivo and the activity of the combination of apatinib and anti-PD-1 in synergistic mouse model of HNSCC. A patient with squamous cell carcinoma of the left tongue with cervical lymph node were received with combined induction treatment of camrelizumab and apatinib to validate the efficacy of neoadjuvant immunotherapy before surgery.
We found that apatinib increased the infiltration of CD8 + T cells and decreased the population of Tregs in a preclinical syngeneic mouse model. The proportions of CD8 + PD1 + T cells were significantly increased in apatinib-treated tumors. The combined treatment of apatinib and anti-PD-1 demonstrated better therapeutic benefit than each treatment alone. The patient with squamous cell carcinoma of the left tongue with cervical lymph node achieved major pathologic response (MPR) after two cycles of combined induction treatment.
Our study demonstrated that apatinib therapy synergized with an anti-PD-1 antibody in preclinical cancer models and in patient with advanced HNSCC. These results provide a new rationale for advancing this neoadjuvant immunotherapy in large scale of clinical trials of HNSCC.
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