CRISPR/Cas9 in Cancer Immunotherapy: Animal Models and Human Clinical Trials

被引：31

作者：

Khalaf, Khalil ^{[1
]}

Janowicz, Krzysztof ^{[1
,2
]}

Dyszkiewicz-Konwinska, Marta ^{[1
,3
]}

Hutchings, Greg ^{[1
,2
]}

Dompe, Claudia ^{[2
]}

Moncrieff, Lisa ^{[2
,4
]}

Jankowski, Maurycy ^{[1
]}

Machnik, Marta ^{[5
]}

Oleksiewicz, Urszula ^{[5
,6
]}

Kocherova, Ievgeniia ^{[1
]}

Petitte, Jim ^{[7
]}

Mozdziak, Paul ^{[8
]}

Shibli, Jamil A. ^{[9
]}

Izycki, Dariusz ^{[5
]}

Jozkowiak, Malgorzata ^{[10
]}

Piotrowska-Kempisty, Hanna ^{[10
]}

Skowronski, Mariusz T. ^{[11
]}

Antosik, Pawel ^{[12
]}

Kempisty, Bartosz ^{[1
,4
,12
,13
,14
]}

机构：

[1] Poznan Univ Med Sci, Dept Anat, PL-60781 Poznan, Poland

[2] Univ Aberdeen, Sch Med Med Sci & Nutr, Aberdeen AB25 2ZD, Scotland

[3] Poznan Univ Med Sci, Dept Biomat & Expt Dent, PL-60812 Poznan, Poland

[4] Poznan Univ Med Sci, Dept Histol & Embryol, PL-60781 Poznan, Poland

[5] Greater Poland Canc Ctr, Dept Canc Diagnost & Immunol, PL-61866 Poznan, Poland

[6] Greater Poland Canc Ctr, Dept Canc Diagnost & Immunol, PL-61866 Poznan, Poland

[7] North Carolina State Univ, Prestage Dept Poultry Sci, Raleigh, NC 27695 USA

[8] North Carolina State Univ, Physiol Grad Program, Raleigh, NC 27695 USA

[9] Univ Guarulhos, Dent Res Div, Dept Periodontol & Oral Implantol, BR-07023070 Guarulhos, Brazil

[10] Poznan Univ Med Sci, Dept Toxicol, PL-61631 Poznan, Poland

[11] Nicolaus Copernicus Univ Torun, Inst Vet Med, Dept Basic & Preclin Sci, PL-87100 Torun, Poland

[12] Nicolaus Copernicus Univ Torun, Dept Vet Surg, PL-87100 Torun, Poland

[13] Univ Hosp, Dept Obstet & Gynecol, Brno 60177, Czech Republic

[14] Masaryk Univ, Brno 60177, Czech Republic

来源：

GENES | 2020年 / 11卷 / 08期

基金：

美国农业部;

关键词：

genome editing; cancer; animal models; experimental oncology; RESISTANCE; GENE; MECHANISMS; SYSTEM; RISK; CAR; DNA;

D O I：

10.3390/genes11080921

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Even though chemotherapy and immunotherapy emerged to limit continual and unregulated proliferation of cancer cells, currently available therapeutic agents are associated with high toxicity levels and low success rates. Additionally, ongoing multi-targeted therapies are limited only for few carcinogenesis pathways, due to continually emerging and evolving mutations of proto-oncogenes and tumor-suppressive genes. CRISPR/Cas9, as a specific gene-editing tool, is used to correct causative mutations with minimal toxicity, but is also employed as an adjuvant to immunotherapy to achieve a more robust immunological response. Some of the most critical limitations of the CRISPR/Cas9 technology include off-target mutations, resulting in nonspecific restrictions of DNA upstream of the Protospacer Adjacent Motifs (PAM), ethical agreements, and the lack of a scientific consensus aiming at risk evaluation. Currently, CRISPR/Cas9 is tested on animal models to enhance genome editing specificity and induce a stronger anti-tumor response. Moreover, ongoing clinical trials use the CRISPR/Cas9 system in immune cells to modify genomes in a target-specific manner. Recently, error-free in vitro systems have been engineered to overcome limitations of this gene-editing system. The aim of the article is to present the knowledge concerning the use of CRISPR Cas9 technique in targeting treatment-resistant cancers. Additionally, the use of CRISPR/Cas9 is aided as an emerging supplementation of immunotherapy, currently used in experimental oncology. Demonstrating further, applications and advances of the CRISPR/Cas9 technique are presented in animal models and human clinical trials. Concluding, an overview of the limitations of the gene-editing tool is proffered.

引用

页码：1 / 19

页数：19

共 101 条

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