Potentiated antitumor effects of APS001F/5-FC combined with anti-PD-1 antibody in a CT26 syngeneic mouse model.
Potentiated antitumor effects of APS001F/5-FC combined with anti-PD-1 antibody in a CT26 syngeneic mouse model.
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APS001F/5-FC 联合抗 PD-1 抗体在 CT26 同系小鼠模型中增强抗肿瘤作用。
DOI：
10.1093/bbb/zbaa057
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Taniguchi S.
中科院分区：
文献类型：
--
作者：
Shioya K;Matsumura T;Seki Y;Shimizu H;Nakamura T;Taniguchi S.
APS 001 F是一株经基因工程改造表达胞嘧啶脱氨酶的长双歧杆菌，该酶可将5-氟胞嘧啶（5-FC）转化为5-氟尿嘧啶。在本研究中，使用CT 26同基因小鼠模型研究了APS 001 F +5-FC（APS 001 F/5-FC）与抗PD-1单克隆抗体联合治疗的抗肿瘤作用。在联合给药中，抗PD-1 mAb之前和之后的APS 001 F/5-FC给药均显示出抗肿瘤作用，并且与未给药对照组相比，生存期延长。与APS 001 F/5-FC单药治疗和抗PD-1 mAb单药治疗相比，联合治疗的生存率显著增加。联合治疗组肿瘤组织中CD 4 +T细胞中调节性T细胞比例下降，而CD 8 +T细胞比例维持不变。综上所述，APS 001 F/5-FC不仅表现出直接的抗肿瘤活性，而且一旦定位于肿瘤的缺氧区域，还表现出免疫调节作用，这使得抗PD-1 mAb能够发挥增强的抗肿瘤作用。
APS001F is a strain ofBifidobacterium longumgenetically engineered to express cytosine deaminase that converts 5-fluorocytosine (5-FC) to 5-fluorouracil. In the present study, antitumor effects of APS001F plus 5-FC (APS001F/5-FC) in combination with anti-PD-1 monoclonal antibody were investigated using a CT26 syngeneic mouse model. Both of dosing of APS001F/5-FC before and after anti-PD-1 mAb in the combination dosing exhibited antitumor effects as well as prolonged survival over the nontreated control. The survival rate in the combination therapy significantly increased over the monotherapy with APS001F/5-FC and that with anti-PD-1 mAb. Regulatory T cells among CD4+T cells in tumor decreased in the combination therapy, while the ratio of CD8+T cells was maintained in all groups. Taken these results together, APS001F/5-FC not only demonstrates a direct antitumor activity, but also immunomodulatory effects once localized in the hypoxic region of the tumor, which allows anti-PD-1 mAb to exert potentiated antitumor effects.
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影响因子：
8
作者：
Markowitz, Geoffrey J.;Havel, Lauren S.;Mittal, Vivek
通讯作者：
Mittal, Vivek
ipilimumab和Nivolumab组合免疫疗法的临床前开发：小鼠肿瘤模型，体外功能研究和cynomolgus猕猴毒理学。
影响因子：
3.7
作者：
Selby MJ;Engelhardt JJ;Johnston RJ;Lu LS;Han M;Thudium K;Yao D;Quigley M;Valle J;Wang C;Chen B;Cardarelli PM;Blanset D;Korman AJ
通讯作者：
Korman AJ
影响因子：
50.3
作者：
Fridlender ZG;Sun J;Kim S;Kapoor V;Cheng G;Ling L;Worthen GS;Albelda SM
通讯作者：
Albelda SM
影响因子：
6.4
作者：
Yazawa, K;Fujimori, M;Taniguchi, S
通讯作者：
Taniguchi, S