Vaccines against human HER2 prevent mammary carcinoma in mice transgenic for human HER2.
Vaccines against human HER2 prevent mammary carcinoma in mice transgenic for human HER2.
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DOI：
10.1186/bcr3602
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发表时间：
2014-01-23
期刊：
影响因子：
--
通讯作者：
Lollini PL
中科院分区：
文献类型：
--
作者：
De Giovanni C;Nicoletti G;Quaglino E;Landuzzi L;Palladini A;Ianzano ML;Dall'Ora M;Grosso V;Ranieri D;Laranga R;Croci S;Amici A;Penichet ML;Iezzi M;Cavallo F;Nanni P;Lollini PL
人类HER2基因转基因小鼠（huHER2）的存在以及容易发生HER2驱动的乳腺癌的小鼠（称为FVB-huHER2小鼠）促使我们在耐受宿主中研究针对人类HER2分子的主动免疫预防策略。FVB-huHER2小鼠接种了il -12佐剂的人HER2阳性癌细胞或携带嵌合人-大鼠HER2序列的DNA疫苗。记录乳腺肿瘤的发病和数量，以评估疫苗的效力。收集小鼠血清，被动转移到异种移植物小鼠体内，以评估其抗肿瘤效果。细胞疫苗和DNA疫苗都显著延缓了肿瘤的发生，导致约65%的小鼠在70周时无肿瘤，而模拟接种了FVB-huHER2的对照组在中位年龄45周时出现乳腺肿瘤。在DNA接种组中，65%的小鼠在大约90周龄时仍然没有肿瘤。在接种疫苗的小鼠中，每只小鼠的乳腺肿瘤数量也显著减少。疫苗打破了对huHER2转基因的免疫耐受，诱导了体液和细胞因子反应。DNA疫苗主要诱导高水平和持续水平的抗huher2抗体，细胞疫苗也诱导干扰素(IFN)-γ的产生。将接种dna疫苗的小鼠血清转移到携带异种移植物的小鼠血清中，可显著抑制人her2阳性癌细胞的生长。在耐受宿主中诱导的抗huher2抗体发挥抗肿瘤活性。
The availability of mice transgenic for the human HER2 gene (huHER2) and prone to the development of HER2-driven mammary carcinogenesis (referred to as FVB-huHER2 mice) prompted us to study active immunopreventive strategies targeting the human HER2 molecule in a tolerant host. FVB-huHER2 mice were vaccinated with either IL-12-adjuvanted human HER2-positive cancer cells or DNA vaccine carrying chimeric human-rat HER2 sequences. Onset and number of mammary tumors were recorded to evaluate vaccine potency. Mice sera were collected and passively transferred to xenograft-bearing mice to assess their antitumor efficacy. Both cell and DNA vaccines significantly delayed tumor onset, leading to about 65% tumor-free mice at 70 weeks, whereas mock-vaccinated FVB-huHER2 controls developed mammary tumors at a median age of 45 weeks. In the DNA vaccinated group, 65% of mice were still tumor-free at about 90 weeks of age. The number of mammary tumors per mouse was also significantly reduced in vaccinated mice. Vaccines broke the immunological tolerance to the huHER2 transgene, inducing both humoral and cytokine responses. The DNA vaccine mainly induced a high and sustained level of anti-huHER2 antibodies, the cell vaccine also elicited interferon (IFN)-γ production. Sera of DNA-vaccinated mice transferred to xenograft-carrying mice significantly inhibited the growth of human HER2-positive cancer cells. Anti-huHER2 antibodies elicited in the tolerant host exert antitumor activity.
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影响因子：
4.4
作者：
Piechocki, MP;Ho, YS;Wei, WZ
通讯作者：
Wei, WZ
影响因子：
11.2
作者：
Nanni, Patrizia;Nicoletti, Giordano;Lollini, Pier-Luigi
通讯作者：
Lollini, Pier-Luigi
影响因子：
4.4
作者：
Rolla, Simona;Nicolo, Chiara;Ria, Francesco
通讯作者：
Ria, Francesco
影响因子：
6.7
作者：
Nanni P;Gatta V;Menotti L;De Giovanni C;Ianzano M;Palladini A;Grosso V;Dall'ora M;Croci S;Nicoletti G;Landuzzi L;Iezzi M;Campadelli-Fiume G;Lollini PL
通讯作者：
Lollini PL
影响因子：
8.4
作者：
Nanni, Patrizia;Nicoletti, Giordano;Lollini, Pier-Luigi
通讯作者：
Lollini, Pier-Luigi