Quantitative evaluation and comparison of two prodrug-activating suicide gene therapies on oral squamous cell carcinoma.
Quantitative evaluation and comparison of two prodrug-activating suicide gene therapies on oral squamous cell carcinoma.
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两种前药激活自杀基因疗法对口腔鳞状细胞癌的定量评估和比较。
DOI：
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Hongyu Yang
中科院分区：
文献类型：
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作者：
Naining Xu;Honglei Tian;Chun Po Fung;Yuntao Lin;Guang Zhu;Shen Yuehong;Hongyu Yang
前药激活型自杀基因治疗(简称PA自杀基因治疗)是将自杀基因导入癌细胞。自杀基因编码的酶无毒，但能够通过将无毒的前体药物转化为有毒化合物来杀死癌细胞。这种方法是一种很有前途的癌症基因治疗方法，可以减少对正常组织的非特异性毒性。然而，在临床前研究中，尚无定量方法评价自杀基因治疗的疗效。这项研究的目的是开发一种新的方法来定量评估和比较前药物激活的自杀基因治疗。本研究是在口腔鳞状细胞癌(OSCC)细胞系CAL-27上进行的。用CRISPR-Cas9将自杀基因整合到CAL-27的rosa26基因座上。用稳定表达单纯疱疹病毒胸苷激酶(TK)或酵母胞嘧啶脱氨酶(CD)的CAL-27细胞株评价和比较PA自杀基因治疗。从有效前药浓度、前药治疗时间和旁观者效应三个方面定量评价PA自杀基因治疗的疗效。这种方法也可以用于不同类型的自杀基因治疗和不同类型的癌症。当前药浓度、治疗时间和自杀基因阳性细胞率(与旁观者效应有关)固定时，可以定量衡量抗癌效果。这一信息对自杀基因治疗的临床前发展非常重要。
Prodrug-activating suicide gene therapy (PA suicide gene therapy for short) for cancer is to introduce cancer cells with suicide genes. The enzyme encoded by suicide gene is not toxic but is able to kill cancer cells by converting a non-toxic prodrug into a toxic compound. This approach is a promising cancer gene therapy that could reduce non-specific toxicity to normal tissue. However, there is no quantitative method to evaluate efficacy of suicide gene therapy in preclinical study. The aim of this study is to develop a new method to quantitatively evaluate and compare prodrug-activating suicide gene therapies. This study was carried out on an oral squamous cell carcinoma (OSCC) cell line CAL-27. Suicide genes were integrated into ROSA26 locus of CAL-27 by CRISPR-Cas9. CAL-27 cell lines stably expressing herpes simplex virus-thymidine kinase (TK) or yeast cytosine deaminase (CD) were used to evaluate and compare PA suicide gene therapies. The efficacies of PA suicide gene therapies were quantitatively evaluated from three aspects: effective prodrug concentration, prodrug treatment time, and bystander effect. This method also could be used for different types of suicide gene therapies and different types of cancer. When the prodrug concentration, treatment time, and rate of suicide gene-positive cells (related to bystander effect) are fixed, anti-cancer effects could be quantitatively measured. This information is important for suicide gene therapy preclinical development.
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影响因子：
16.1
作者：
Karjoo Z;Chen X;Hatefi A
通讯作者：
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影响因子：
11.2
作者：
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影响因子：
11.2
作者：
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通讯作者：
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影响因子：
12.8
作者：
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通讯作者：
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影响因子：
4.3
作者：
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通讯作者：
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