Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMax.
Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMax.
复制标题
DOI：
10.1186/1479-5876-5-20
复制
发表时间：
2007-04-23
影响因子：
7.4
通讯作者：
Daftarian P
中科院分区：
文献类型：
--
作者：
Mansour M;Pohajdak B;Kast WM;Fuentes-Ortega A;Korets-Smith E;Weir GM;Brown RG;Daftarian P
已知黑色素瘤肿瘤表达通常诱导短持续时间的弱免疫应答的抗原。黑色素瘤细胞表达肿瘤相关抗原p53和TRP 2，提高了在治疗性疫苗中同时靶向一种以上抗原的可能性。在这份报告中，我们表明VacciMax®（VM），一种新型的基于脂质体的疫苗递送平台，可以增加黑色素瘤相关抗原的免疫原性，从而消除肿瘤。在肿瘤植入后6天，用合成肽（修饰的p53：232-240、TRP-2：181-188和PADRE）和CpG的混合物皮下接种携带B16-F10黑素瘤肿瘤的C57 BL/6小鼠。监测肿瘤生长并通过ELISPOT测定抗原特异性脾细胞应答。在VM中配制的疫苗在单次接种后增加了TRP 2特异性和p53特异性产生IFN-γ的脾细胞的数量。没有VM配制的疫苗仅导致针对一个CTL表位的产生IFN-γ的脾细胞增强（TRP 2：180-188），表明VM克服了抗原优势并增强了多个表位的免疫原性。用VM中配制的TRP 2和p53肽对携带6天大B16-F10肿瘤的小鼠进行疫苗接种，成功根除了所有小鼠的肿瘤。含有除脂质体以外的所有成分的对照疫苗导致不超过20%的小鼠的肿瘤根除。单次施用VM能够诱导对多种肿瘤相关抗原的有效CTL应答。产生的应答能够排斥6天龄的B16-F10肿瘤。
Melanoma tumors are known to express antigens that usually induce weak immune responses of short duration. Expression of both tumor-associated antigens p53 and TRP2 by melanoma cells raises the possibility of simultaneously targeting more than one antigen in a therapeutic vaccine. In this report, we show that VacciMax® (VM), a novel liposome-based vaccine delivery platform, can increase the immunogenicity of melanoma associated antigens, resulting in tumor elimination. C57BL/6 mice bearing B16-F10 melanoma tumors were vaccinated subcutaneously 6 days post tumor implantation with a mixture of synthetic peptides (modified p53: 232–240, TRP-2: 181–188 and PADRE) and CpG. Tumor growth was monitored and antigen-specific splenocyte responses were assayed by ELISPOT. Vaccine formulated in VM increased the number of both TRP2- and p53-specific IFN-γ producing splenocytes following a single vaccination. Vaccine formulated without VM resulted only in enhanced IFN-γ producing splenocytes to one CTL epitopes (TRP2:180–188), suggesting that VM overcomes antigen dominance and enhances immunogenicity of multiple epitopes. Vaccination of mice bearing 6-day old B16-F10 tumors with both TRP2 and p53-peptides formulated in VM successfully eradicated tumors in all mice. A control vaccine which contained all ingredients except liposomes resulted in eradication of tumors in no more than 20% of mice. A single administration of VM is capable of inducing an effective CTL response to multiple tumor-associated antigens. The responses generated were able to reject 6-day old B16-F10 tumors.
登录
查看更多内容
影响因子：
3.4
作者：
Brown, RG;Bowen, WD;Pohajdak, B
通讯作者：
Pohajdak, B
影响因子：
8
作者：
Kichina, JV;Rauth, S;Gudkov, AV
通讯作者：
Gudkov, AV
影响因子：
10.3
作者：
MCGREGOR, JM;YU, CCW;MACDONALD, DM
通讯作者：
MACDONALD, DM
影响因子：
82.9
作者：
Rosenberg, SA;Yang, JC;White, DE
通讯作者：
White, DE
影响因子：
4.4
作者：
Bellone, M;Cantarella, D;Dellabona, P
通讯作者：
Dellabona, P