Cdk5 knocking out mediated by CRISPR-Cas9 genome editing for PD-L1 attenuation and enhanced antitumor immunity

Deng, Huan; Tan, Songwei; Gao, Xueqin; Zou, Chenming; Xu, Chenfeng; Tu, Kun; Song, Qingle; Fan, Fengjuan; Huang, Wei; Zhang, Zhiping

doi:10.1016/j.apsb.2019.07.004

Cited by 65 publications

(66 citation statements)

References 51 publications

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“…131,132 CRISPR knockout of CDK5 has also been shown to downregulate PD-L1 expression, inhibiting tumour growth in vitro and in vivo. 133,134 shRNAmediated knockdown of CD155 has also been observed to inhibit the growth of in vitro and in vivo BC models, highlighting its potential in BC therapy. 135 Knockdown of checkpoint proteins may be used to enhance the efficacy of chimeric antigen receptor (CAR) T-cells, which express CARs recognising tumourassociated antigens (TAAs).…”

Section: Immunotherapymentioning

confidence: 99%

Therapeutic applications of CRISPR/Cas9 in breast cancer and delivery potential of gold nanomaterials

Padayachee

Singh

2020

Nanobiomedicine

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Globally, approximately 1 in 4 cancers in women are diagnosed as breast cancer (BC). Despite significant advances in the diagnosis and therapy BCs, many patients develop metastases or relapses. Hence, novel therapeutic strategies are required, that can selectively and efficiently kill malignant cells. Direct targeting of the genetic and epigenetic aberrations that occur in BC development is a promising strategy to overcome the limitations of current therapies, which target the tumour phenotype. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system, composed of only an easily modifiable single guide RNA (sgRNA) sequence bound to a Cas9 nuclease, has revolutionised genome editing due to its simplicity and efficiency compared to earlier systems. CRISPR/Cas9 and its associated catalytically inactivated dCas9 variants facilitate the knockout of overexpressed genes, correction of mutations in inactivated genes, and reprogramming of the epigenetic landscape to impair BC growth. To achieve efficient genome editing in vivo, a vector is required to deliver the components to target cells. Gold nanomaterials, including gold nanoparticles and nanoclusters, display many advantageous characteristics that have facilitated their widespread use in theranostics, as delivery vehicles, and imaging and photothermal agents. This review highlights the therapeutic applications of CRISPR/Cas9 in treating BCs, and briefly describes gold nanomaterials and their potential in CRISPR/Cas9 delivery.

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Section: Immunotherapymentioning

confidence: 99%

Therapeutic applications of CRISPR/Cas9 in breast cancer and delivery potential of gold nanomaterials

Padayachee

Singh

2020

Nanobiomedicine

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“…Resistance to immune checkpoint blocking therapy is a prevalent phenomenon observed in many tumors, in particular, “cold” tumors, a term attributed to tumors whose microenvironment is not appropriate for infiltration of tumor-specific T-cells [ 131 ]. In this regard, Tu et al developed a weak-acidity-responsive nanoparticle for efficient delivery of cyclin-dependent kinase 5-targeting CRISPR-Cas9 (to suppress PD-L1 expression on tumor cells [ 132 ]) and paclitaxel (to trigger anti-tumor immune responses) to the tumor site, and thereby succeeded to exchange tumor microenvironment from “cold” to “hot” and to inhibit tumor growth in melanoma and colorectal cancer mice models [ 133 ].…”

Section: The Deluxe Zone Of Cancer Therapy Where Crispr Meets Immunomentioning

confidence: 99%

CRISPR-Cas, a robust gene-editing technology in the era of modern cancer immunotherapy

et al. 2020

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Cancer immunotherapy has been emerged as a promising strategy for treatment of a broad spectrum of malignancies ranging from hematological to solid tumors. One of the principal approaches of cancer immunotherapy is transfer of natural or engineered tumor-specific T-cells into patients, a so called “adoptive cell transfer”, or ACT, process. Construction of allogeneic T-cells is dependent on the employment of a gene-editing tool to modify donor-extracted T-cells and prepare them to specifically act against tumor cells with enhanced function and durability and least side-effects. In this context, CRISPR technology can be used to produce universal T-cells, equipped with recombinant T cell receptor (TCR) or chimeric antigen receptor (CAR), through multiplex genome engineering using Cas nucleases. The robust potential of CRISPR-Cas in preparing the building blocks of ACT immunotherapy has broaden the application of such therapies and some of them have gotten FDA approvals. Here, we have collected the last investigations in the field of immuno-oncology conducted in partnership with CRISPR technology. In addition, studies that have addressed the challenges in the path of CRISPR-mediated cancer immunotherapy, as well as pre-treatment applications of CRISPR-Cas have been mentioned in detail.

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“…However, rapid degradation of nucleic acids by nucleases and their inadequate ability to internalize into the cells and crossing nuclear membrane are the main challenges [75]. Poly (b-amino esters), a cationic polymer that has been used extensively in gene delivery due to their high loading capacity and safety, was recently exploited to deliver the CRISPR-Cas9 genome editing system to knockout cyclindependent kinase 5 (cdk5) in vivo [76]. It was observed that deletion of cdk5 downregulates PD-L1 and triggers strong T cell-mediated immune responses in TME.…”

Section: Silence or Knockout Of Genes Involved In Tumor Growth By Nanmentioning

confidence: 99%

“…It was observed that deletion of cdk5 downregulates PD-L1 and triggers strong T cell-mediated immune responses in TME. Consequently, tumor growth and metastasis are inhibited in 4T1 tumor-bearing mice [76]. Adenosine mediates immunosuppression within TME via binding its receptors on immune cells.…”

Section: Silence or Knockout Of Genes Involved In Tumor Growth By Nanmentioning

confidence: 99%

Emerging nanomedicines for effective breast cancer immunotherapy

2020

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Breast cancer continues to be the most frequently diagnosed malignancy among women, putting their life in jeopardy. Cancer immunotherapy is a novel approach with the ability to boost the host immune system to recognize and eradicate cancer cells with high selectivity. As a promising treatment, immunotherapy can not only eliminate the primary tumors, but also be proven to be effective in impeding metastasis and recurrence. However, the clinical application of cancer immunotherapy has faced some limitations including generating weak immune responses due to inadequate delivery of immunostimulants to the immune cells as well as uncontrolled modulation of immune system, which can give rise to autoimmunity and nonspecific inflammation. Growing evidence has suggested that nanotechnology may meet the needs of current cancer immunotherapy. Advanced biomaterials such as nanoparticles afford a unique opportunity to maximize the efficiency of immunotherapy and significantly diminish their toxic side-effects. Here we discuss recent advancements that have been made in nanoparticle-involving breast cancer immunotherapy, varying from direct activation of immune systems through the delivery of tumor antigens and adjuvants to immune cells to altering immunosuppression of tumor environment and combination with other conventional therapies.

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Cdk5 knocking out mediated by CRISPR-Cas9 genome editing for PD-L1 attenuation and enhanced antitumor immunity

Cited by 65 publications

References 51 publications

Therapeutic applications of CRISPR/Cas9 in breast cancer and delivery potential of gold nanomaterials

Therapeutic applications of CRISPR/Cas9 in breast cancer and delivery potential of gold nanomaterials

CRISPR-Cas, a robust gene-editing technology in the era of modern cancer immunotherapy

Emerging nanomedicines for effective breast cancer immunotherapy

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