Lentivector immunization stimulates potent CD8 T cell responses against melanoma self-antigen tyrosinase-related protein 1 and generates antitumor immunity in mice.
Lentivector immunization stimulates potent CD8 T cell responses against melanoma self-antigen tyrosinase-related protein 1 and generates antitumor immunity in mice.
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DOI：
10.4049/jimmunol.0900008
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发表时间：
2009-05-15
期刊：
影响因子：
--
通讯作者：
He Y
中科院分区：
文献类型：
--
作者：
Liu Y;Peng Y;Mi M;Guevara-Patino J;Munn DH;Fu N;He Y
Recombinant lentivector immunization has been demonstrated to induce potent CD8 T cell responses in vivo. In this study, we investigated whether lentivector delivering a self/tumor Ag, tyrosinase related protein 1 (TRP1), could stimulate effective antitumor T cell responses. We found that immunization with lentivector expressing mutated TRP1 Ag elicited potent CD8 T cell responses against multiple TRP1 epitopes. Importantly, the activated CD8 T cells effectively recognize wild-type TRP1 epitopes. At peak times, as many as 10% of CD8 T cells were effector cells against TRP1 Ag. These cells killed wild-type TRP1 peptide-pulsed target cells in vivo and produced IFN-γ after ex vivo stimulation. The CD8 T cell responses were long-lasting (3– 4 wk). Immunized mice were protected from B16 tumor cell challenge. In a therapeutic setting, lentivector immunization induced potent CD8 T cell responses in tumor bearing mice. The number of infiltrating T cells and the ratio of CD8/CD4 were dramatically increased in the tumors of immunized mice. The tumor-infiltrating CD8 T cells were functional and produced IFN-γ. The potent CD8 T cell responses stimulated by lentivector immunization eliminated small 3-day s.c. B16 tumors and strongly inhibited the growth of more established 5-day tumors. These studies demonstrate that genetic immunization with lentivector expressing mutated self/tumor Ag can generate potent CD8 T cell immune responses and antitumor immunity that prevent and inhibit B16 tumor growth, suggesting that lentivector immunization has the potential for tumor immunotherapy and immune prevention.
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影响因子：
5.1
作者：
Dullaers, M;Van Meirvenne, S;Breckpot, K
通讯作者：
Breckpot, K
影响因子：
11.2
作者：
Blank, C;Brown, I;Gajewski, TF
通讯作者：
Gajewski, TF
影响因子：
11.2
作者：
Hou, De-Yan;Muller, Alexander J.;Munn, David H.
通讯作者：
Munn, David H.
影响因子：
5.4
作者：
Casado, Javier Garcia;Janda, Jozef;Levy, Frederic
通讯作者：
Levy, Frederic
GP100/PMEL 17是一种鼠肿瘤排斥抗原：使用高亲和力，改变肽配体改变的“自我”反应性，肿瘤T细胞。
DOI：
10.1084/jem.188.2.277
发表时间：
1998-07-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Overwijk WW;Tsung A;Irvine KR;Parkhurst MR;Goletz TJ;Tsung K;Carroll MW;Liu C;Moss B;Rosenberg SA;Restifo NP
通讯作者：
Restifo NP