CRISPR/Cas9 Gene-Editing in Cancer Immunotherapy: Promoting the Present Revolution in Cancer Therapy and Exploring More

Ou, Xuejin; Ma, Qian; Yin, Wei; Ma, Xuelei; He, Zhiyao

doi:10.3389/fcell.2021.674467

Cited by 36 publications

(30 citation statements)

References 121 publications

(136 reference statements)

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“…New immunomodulatory targets have also been identified in vivo immuno-CRISPR/Cas9 screens and PTPN2 is among one of the top hits ( 75 ). CRISPR-mediated knockout of PTPN2 sensitized response towards anti-PD1 treatment, by enhancing IFNγ-mediated antigen presentation and increasing cytotoxic Tim-3+ CD8+ Tcells ( 76 , 77 ).…”

Section: Targeted Agents Tested In Combination With Icis In Hncmentioning

confidence: 99%

Rational Combinations of Targeted Therapy and Immune Checkpoint Inhibitors in Head and Neck Cancers

2022

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Immunotherapy, especially the immune checkpoint inhibitors (ICIs) such as the pembrolizumab and nivolumab have contributed to significant improvements in treatment outcomes and survival of head and neck cancer (HNC) patients. Still, only a subset of patients benefits from ICIs and hence the race is on to identify combination therapies that could improve response rates. Increasingly, genetic alterations that occur within cancer cells have been shown to modulate the tumor microenvironment resulting in immune evasion, and these have led to the emergence of trials that rationalize a combination of targeted therapy with immunotherapy. In this review, we aim to provide an overview of the biological rationale and current strategies of combining targeted therapy with the approved ICIs in HNC. We summarize the ongoing combinatorial clinical trials and discuss emerging immunomodulatory targets. We also discuss the challenges and gaps that have yet to be addressed, as well as future perspectives in combining these different drug classes.

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Section: Targeted Agents Tested In Combination With Icis In Hncmentioning

confidence: 99%

Rational Combinations of Targeted Therapy and Immune Checkpoint Inhibitors in Head and Neck Cancers

2022

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“…Currently, although emerging tumor treatment methods have made some progress, the effect of them is still difficult to be satisfied in the clinical treatment (Lai et al, 2021;Mo et al, 2021;Ou et al, 2021;Wang and Bai, 2021). Ferroptosis has the potential ability to make the synergy effect with conventional or emerging tumor therapy which brings more spark in the treatment of different tumors (Xue et al, 2020).…”

Section: Emerging Nanomedicine Based On Ferroptosis and Conventional Or Emerging Tumor Therapymentioning

confidence: 99%

Ferroptosis-Inducing Nanomedicine for Cancer Therapy

Wang

Liu

et al. 2021

Front. Pharmacol.

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Ferroptosis, a new iron- and reactive oxygen species–dependent form of regulated cell death, has attracted much attention in the therapy of various types of tumors. With the development of nanomaterials, more and more evidence shows the potential of ferroptosis combined with nanomaterials for cancer therapy. Recently, there has been much effort to develop ferroptosis-inducing nanomedicine, specially combined with the conventional or emerging therapy. Therefore, it is necessary to outline the previous work on ferroptosis-inducing nanomedicine and clarify directions for improvement and application to cancer therapy in the future. In this review, we will comprehensively focus on the strategies of cancer therapy based on ferroptosis-inducing nanomedicine currently, elaborate on the design ideas of synthesis, analyze the advantages and limitations, and finally look forward to the future perspective on the emerging field.

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“…Nevertheless, precise methods including high-throughput sequencing and multi-omics analyses are highly desirable to detect sporadic off-target effects. Also, anti-Cas antibodies and anti-Cas T-cells have been detected ( 89 , 90 ). Blood pharming supports the safe application of genetic engineered products, as the target for genetic engineering is cell source (e.g.…”

Section: Strategies For Genetic Engineeringmentioning

confidence: 99%

Generation of HLA Universal Megakaryocytes and Platelets by Genetic Engineering

Figueiredo

Blasczyk

2021

Front. Immunol.

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Patelet transfusion refractoriness remains a relevant hurdle in the treatment of severe alloimmunized thrombocytopenic patients. Antibodies specific for the human leukocyte antigens (HLA) class I are considered the major immunological cause for PLT transfusion refractoriness. Due to the insufficient availability of HLA-matched PLTs, the development of new technologies is highly desirable to provide an adequate management of thrombocytopenia in immunized patients. Blood pharming is a promising strategy not only to generate an alternative to donor blood products, but it may offer the possibility to optimize the therapeutic effect of the produced blood cells by genetic modification. Recently, enormous technical advances in the field of in vitro production of megakaryocytes (MKs) and PLTs have been achieved by combining progresses made at different levels including identification of suitable cell sources, cell pharming technologies, bioreactors and application of genetic engineering tools. In particular, use of RNA interference, TALEN and CRISPR/Cas9 nucleases or nickases has allowed for the generation of HLA universal PLTs with the potential to survive under refractoriness conditions. Genetically engineered HLA-silenced MKs and PLTs were shown to be functional and to have the capability to survive cell- and antibody-mediated cytotoxicity using in vitro and in vivo models. This review is focused on the methods to generate in vitro genetically engineered MKs and PLTs with the capacity to evade allogeneic immune responses.

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CRISPR/Cas9 Gene-Editing in Cancer Immunotherapy: Promoting the Present Revolution in Cancer Therapy and Exploring More

Cited by 36 publications

References 121 publications

Rational Combinations of Targeted Therapy and Immune Checkpoint Inhibitors in Head and Neck Cancers

Rational Combinations of Targeted Therapy and Immune Checkpoint Inhibitors in Head and Neck Cancers

Ferroptosis-Inducing Nanomedicine for Cancer Therapy

Generation of HLA Universal Megakaryocytes and Platelets by Genetic Engineering

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