Treatment of HPV-Related Uterine Cervical Cancer with a Third-Generation Oncolytic Herpes Simplex Virus in Combination with an Immune Checkpoint Inhibitor.
Treatment of HPV-Related Uterine Cervical Cancer with a Third-Generation Oncolytic Herpes Simplex Virus in Combination with an Immune Checkpoint Inhibitor.
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DOI：
10.3390/ijms24031988
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发表时间：
2023-01-19
影响因子：
5.6
通讯作者：
Baba, Tsukasa
中科院分区：
文献类型：
--
作者：
Kagabu, Masahiro;Yoshino, Naoto;Murakami, Kazuyuki;Kawamura, Hideki;Sasaki, Yutaka;Muraki, Yasushi;Baba, Tsukasa
关键词：
宫颈癌是女性最常见的癌症之一。目前正在研究使用免疫检查点抑制剂（ICI）的新疗法用于宫颈癌;然而，它们的疗效目前还不够。溶瘤病毒治疗可以增加肿瘤免疫原性，增强ICIs的抗肿瘤作用。在这份报告中，三突变溶瘤疱疹病毒（T-01）与ICI的人乳头瘤病毒（HPV）相关的宫颈癌的治疗潜力进行了评估，使用双边同基因小鼠模型。肿瘤内（i.t.）T-01和皮下（s.c.）在T-01注射侧，抗程序性细胞死亡配体1（PD-L1）抗体（Ab）的施用等同于单独抗PD-L1 Ab。此外，与单药治疗相比，联合治疗对T-01非注射侧无显著抗肿瘤作用。联合治疗显著增加了肿瘤中肿瘤特异性T细胞的数量。虽然T-01不能从接受联合治疗的肿瘤中分离，但它可以在T-01单药治疗后分离。此外，T-01对刺激的T细胞具有细胞毒性作用。这些结果表明T-01和抗PD-L1 Ab部分抵消，因此应谨慎考虑合并给药。
Cervical cancer is one of the most common cancers in women. The development of new therapies with immune checkpoint inhibitors (ICIs) is being investigated for cervical cancer; however, their efficacy is not currently sufficient. Oncolytic virus therapy can increase tumor immunogenicity and enhance the antitumor effect of ICIs. In this report, the therapeutic potential of a triple-mutated oncolytic herpes virus (T-01) with an ICI for human papillomavirus (HPV)-related cervical cancer was evaluated using a bilateral syngeneic murine model. The efficacy of intratumoral (i.t.) administration with T-01 and subcutaneous (s.c.) administration of anti-programmed cell death ligand 1 (PD-L1) antibody (Ab) was equivalent to that of anti-PD-L1 Ab alone on the T-01-injected side. Moreover, combination therapy had no significant antitumor effect compared to monotherapy on the T-01-non-injected side. Combination therapy significantly increased the number of tumor specific T cells in the tumor. While T-01 could not be isolated from tumors receiving combination therapy, it could be isolated following T-01 monotherapy. Furthermore, T-01 had a cytotoxic effect on stimulated T cells. These results suggest that T-01 and anti-PD-L1 Ab partially counteract and therefore concomitant administration should be considered with caution.
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影响因子：
30.5
作者：
Latchman, Y;Wood, CR;Freeman, GJ
通讯作者：
Freeman, GJ
DOI：
10.1177/2051013617717914
发表时间：
2017-06-01
期刊：
Therapeutic advances in vaccines
影响因子：
--
作者：
Smola, Sigrun;Trimble, Connie;Stern, Peter L
通讯作者：
Stern, Peter L
影响因子：
3.7
作者：
Sasaki Y;Hagiwara K;Kakisaka M;Yamada K;Murakami T;Aida Y
通讯作者：
Aida Y
DOI：
10.1016/j.omto.2020.03.022
发表时间：
2020-06-26
期刊：
MOLECULAR THERAPY ONCOLYTICS
影响因子：
--
作者：
Sugawara, Kotaro;Iwai, Miwako;Todo, Tomoki
通讯作者：
Todo, Tomoki
影响因子：
45.3
作者：
Chung, Hyun Cheol;Ros, Willeke;Leary, Alexandra
通讯作者：
Leary, Alexandra