Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy.
Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy.
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DOI：
10.1038/s41598-021-94250-0
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发表时间：
2021-07-19
影响因子：
4.6
通讯作者：
Badiee A
中科院分区：
文献类型：
--
作者：
Yazdani M;Gholizadeh Z;Nikpoor AR;Mohamadian Roshan N;Jaafari MR;Badiee A
缺乏预先存在的肿瘤浸润性T细胞导致对程序性细胞死亡蛋白1(PD-1)阻断治疗的抵抗，可以通过联合抗癌疫苗和CpG-ODN增加T细胞的扩增和浸润来解决。因此，我们制备了一种体外树突状细胞(DC)疫苗，用低剂量脂质体或非脂质体gp100抗原(2.8微克)加CpG-ODN(800微克)冲击，并结合抗PD-1治疗评估其抗肿瘤活性。我们的结果表明，脂质体+CpG-ODN冲击的DC与抗PD-1抗体相结合效果更好，治疗小鼠肿瘤部位的TJeff/Treg TIL显著增加，干扰素-γ的表达水平显著增加4倍，这以CD8T细胞依赖的方式逆转了对PD-1阻断的抵抗。此外，与非脂质体多肽+CpG-ODN或单一治疗的脂质体多肽制剂相比，这种组合还导致了黑色素瘤小鼠显著的肿瘤缓解和存活率延长。我们的结果为设计联合方案以提高免疫检查点阻滞剂的疗效提供了必要的见解，即使是通过小剂量的多肽和CpG-ODN也是如此。
Lack of pre-existing tumor infiltrated T cells resulting in resistance to programmed cell death protein 1 (PD-1) blockade therapies can be solved by combining with anti-cancer vaccines and CpG-ODN in increasing T cell expansion and infiltration. Therefore, we prepared an ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of either liposomal or non-liposomal gp100 antigen (2.8 µg) plus CpG-ODN (800 ng) formulations and evaluated its anti-tumor activity in combination with anti-PD-1 therapy. Our results showed a combination of liposomal peptide plus CpG-ODN pulsed DC with anti-PD-1 antibody was more efficacious, as evidenced by a significant increase in Teff/Treg TILs with a marked fourfold elevation of IFN-γ expression level in the tumor site of treated mice which reversed resistance to PD-1 blockade in a CD8 T cell-dependent manner. Furthermore, this combination also led to a remarkable tumor remission and prolonged survival rate in melanoma-bearing mice compared to non-liposomal peptide plus CpG-ODN or single-treated liposomal peptide formulations. Our results provide essential insights to devise combining regimens to improve the efficacy of immune checkpoint blockers even by a low dose of peptide and CpG-ODN.
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DOI：
10.1038/nrc3258
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.8
作者：
Shirota H;Tross D;Klinman DM
通讯作者：
Klinman DM
影响因子：
28.2
作者：
Chen PL;Roh W;Reuben A;Cooper ZA;Spencer CN;Prieto PA;Miller JP;Bassett RL;Gopalakrishnan V;Wani K;De Macedo MP;Austin-Breneman JL;Jiang H;Chang Q;Reddy SM;Chen WS;Tetzlaff MT;Broaddus RJ;Davies MA;Gershenwald JE;Haydu L;Lazar AJ;Patel SP;Hwu P;Hwu WJ;Diab A;Glitza IC;Woodman SE;Vence LM;Wistuba II;Amaria RN;Kwong LN;Prieto V;Davis RE;Ma W;Overwijk WW;Sharpe AH;Hu J;Futreal PA;Blando J;Sharma P;Allison JP;Chin L;Wargo JA
通讯作者：
Wargo JA
影响因子：
12.4
作者：
Lai C;Duan S;Ye F;Hou X;Li X;Zhao J;Yu X;Hu Z;Tang Z;Mo F;Yang X;Lu X
通讯作者：
Lu X
影响因子：
7.4
作者：
Mansour M;Pohajdak B;Kast WM;Fuentes-Ortega A;Korets-Smith E;Weir GM;Brown RG;Daftarian P
通讯作者：
Daftarian P