Treatment of HPV-Related Uterine Cervical Cancer with a Third-Generation Oncolytic Herpes Simplex Virus in Combination with an Immune Checkpoint Inhibitor

被引:8
作者
Kagabu, Masahiro [1 ]
Yoshino, Naoto [2 ]
Murakami, Kazuyuki [1 ]
Kawamura, Hideki [1 ]
Sasaki, Yutaka [2 ]
Muraki, Yasushi [2 ]
Baba, Tsukasa [1 ]
机构
[1] Iwate Med Univ, Sch Med, Dept Obstet & Gynecol, Shiwa, Iwate 0283695, Japan
[2] Iwate Med Univ, Sch Med, Dept Microbiol, Div Infect Dis & Immunol, Shiwa, Iwate 0283694, Japan
基金
日本学术振兴会;
关键词
cervical cancer; oncolytic virus; herpes simplex virus; oncolytic viral therapy; immune checkpoint inhibitor; VECTOR G47-DELTA; THERAPY; EFFICACY; SAFETY; MODELS;
D O I
10.3390/ijms24031988
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:11
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