Gregor Polly D, Wolchok Jedd D, Ferrone Cristina R, Buchinshky Heidi, Guevara-Patiño Jose A, Perales Miguel-Angel, Mortazavi Fariborz, Bacich Dean, Heston Warren, Latouche Jean-Baptiste, Sadelain Michel, Allison James P, Scher Howard I, Houghton Alan N
Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Vaccine. 2004 Apr 16;22(13-14):1700-8. doi: 10.1016/j.vaccine.2003.10.048.
Xenogeneic DNA vaccination can elicit tumor immunity through T cell and antibody-dependent effector mechanisms. Blockade of CTLA-4 engagement with B7 expressed on APCs has been shown to enhance T cell-dependent immunity. We investigated whether CTLA-4 blockade could increase T-cell responses and tumor immunity elicited by DNA vaccines. CTLA-4 blockade enhanced B16 tumor rejection in mice immunized against the melanoma differentiation antigens tyrosinase-related protein 2 and gp100, and this effect was stronger when anti-CTLA-4 was administered with booster vaccinations. CTLA-4 blockade also increased the T-cell responses to prostate-specific membrane antigen (PSMA) when given with the second or third vaccination. Based on these pre-clinical studies, we suggest that anti-CTLA-4 should be tested with xenogeneic DNA vaccines against cancer and that special attention should be given to sequence and schedule of administration.
异种DNA疫苗接种可通过T细胞和抗体依赖性效应机制引发肿瘤免疫。已证明阻断CTLA-4与抗原呈递细胞（APC）上表达的B7的结合可增强T细胞依赖性免疫。我们研究了CTLA-4阻断是否能增强DNA疫苗引发的T细胞反应和肿瘤免疫。CTLA-4阻断增强了针对黑色素瘤分化抗原酪氨酸酶相关蛋白2和gp100免疫的小鼠对B16肿瘤的排斥反应，当抗CTLA-4与加强疫苗接种同时给药时，这种效果更强。当与第二次或第三次疫苗接种同时给予时，CTLA-4阻断也增加了对前列腺特异性膜抗原（PSMA）的T细胞反应。基于这些临床前研究，我们建议应使用抗CTLA-4与异种DNA癌症疫苗进行试验，并应特别注意给药顺序和时间表。
