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首页> 外文期刊>Journal of immunotherapy >Direct injection of protamine-protected mRNA: results of a phase 1/2 vaccination trial in metastatic melanoma patients.
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Direct injection of protamine-protected mRNA: results of a phase 1/2 vaccination trial in metastatic melanoma patients.

机译：直接注射鱼精蛋白保护的mRNA：转移性黑色素瘤患者1/2期免疫接种试验的结果。

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In mice, injection of messenger RNA (mRNA) coding for tumor-associated antigens can induce antitumor immune responses and therefore offers a broadly applicable immunotherapy approach. We injected intradermally protamine-stabilized mRNAs coding for Melan-A, Tyrosinase, gp100, Mage-A1, Mage-A3, and Survivin in 21 metastatic melanoma patients. In 10 patients keyhole limpet hemocyanin (KLH) was added to the vaccine. Granulocyte macrophage colony-stimulating factor was applied as an adjuvant. Endpoints were toxicity and immune responses. No adverse events more than grade II have been observed. During treatment the frequency of Foxp3+/CD4+ regulatory T cells was significantly decreased upon mRNA vaccination in peripheral blood of the patients in the KLH arm, whereas myeloid suppressor cells (CD11b+HLA-DR lo monocytes) were reduced in the patients not receiving KLH. A reproducible increase of vaccine-directed T cells was observed in 2 of 4 immunologically evaluable patients. One of 7 patients with measurable disease showed a complete response. In conclusion, we show here that direct injection of protamine-protected mRNA is feasible and safe. The significant influence of the treatment on the frequency of immunosuppressive cells, the increase of vaccine-directed T cells upon treatment in a subset of patients together with the demonstration of a complete clinical response encourage further clinical investigation of the protamine-mRNA vaccine.
机译：在小鼠中，注射编码肿瘤相关抗原的信使RNA（mRNA）可以诱导抗肿瘤免疫反应，因此提供了广泛适用的免疫疗法。我们在21名转移性黑素瘤患者中注射了真皮内鱼精蛋白稳定的mRNA，它们编码Melan-A，酪氨酸酶，gp100，Mage-A1，Mage-A3和Survivin。在10例患者的疫苗中加入了匙孔戚血蓝蛋白（KLH）。粒细胞巨噬细胞集落刺激因子用作佐剂。终点是毒性和免疫反应。没有观察到超过II级的不良事件。在治疗期间，KLH组患者外周血中的mRNA疫苗接种后，Foxp3 + / CD4 +调节性T细胞的频率显着降低，而未接受KLH的患者骨髓抑制细胞（CD11b + HLA-DR lo单核细胞）减少。在4个具有免疫学评估的患者中，有2个观察到了针对疫苗的T细胞的可再现增加。 7例可测量疾病患者中有1例显示完全缓解。总之，我们在这里表明直接注射鱼精蛋白保护的mRNA是可行和安全的。该治疗对免疫抑制细胞频率的显着影响，在一部分患者中治疗后疫苗导向的T细胞的增加以及完整临床反应的证明，鼓励了对鱼精蛋白-mRNA疫苗的进一步临床研究。

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