Development of oncolytic virotherapy: from genetic modification to combination therapy

Lan, Qiaoshuai; Xia, Shuai; Wang, Qian; Xu, Wei; Huang, Haiyan; Jiang, Shibo; Lu, Lu

doi:10.1007/s11684-020-0750-4

Cited by 40 publications

(42 citation statements)

References 231 publications

(250 reference statements)

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“…[36][37][38][39] Finally, oncolytic viruses are attracting growing interest as versatile cancer therapeutics. [40][41][42][43][44][45] They can selectively replicate in cancer cells, eventually inducing cell-lysis and further activating antitumor immune response. 46,47 Promising oncolytic vectors are genetically modified from adenovirus, herpes virus, reovirus and measles virus.…”

Section: Viral Vectorsmentioning

confidence: 99%

Materials promoting viral gene delivery

Kaygisiz

Synatschke

2020

Biomater. Sci.

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Section: Viral Vectorsmentioning

confidence: 99%

Materials promoting viral gene delivery

Kaygisiz

Synatschke

2020

Biomater. Sci.

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“…Oncolytic viruses may constitute the next breakthrough in cancer immunotherapy [ 456 ]. They comprise DNA and RNA viruses, which can be wild-type (e.g., coxsackie virus, reovirus) or genetically modified (e.g., herpes simplex virus (HSV), adenovirus, vaccinia virus) [ 457 ]. Oncolytic viruses selectively replicate in tumor tissue while destroying it [ 14 , 458 , 459 , 460 ].…”

Section: Manipulating the Tme Using Therapeutic Nucleic Acidsmentioning

confidence: 99%

“…However, the clinical efficacy fell short of the expectations, but safety and synergism with standard cancer treatments could be demonstrated [ 464 ]. Subsequent generations of oncolytic viruses have been developed by genetic engineering to enhance selectivity and efficiency while maintaining or even improving safety [ 457 , 459 , 465 , 466 ] ( Figure 4 ). Tumor selectivity can be enhanced at several levels (transduction, transcription, translation, post-translation) as well as via oncogenic targeting or insertion of miRNA targeting sequences [ 465 , 467 ].…”

Section: Manipulating the Tme Using Therapeutic Nucleic Acidsmentioning

confidence: 99%

“…Oncolytic and immunogenic efficacy can be increased by insertion of certain transgenes encoding (i) enzymes that convert pro-drugs to cytotoxic products (e.g., HSV-TK or cytosine deaminase), (ii) immunostimulatory cytokines (e.g., GM-CSF or IL-12), or (iii) TME/ECM-modifying peptides and enzymes (e.g., MMP-9 or the anti-angiogenic peptide angiostatin) [ 468 ]. Safety can be ensured by mutations in pathogenic and virulence genes as well as in genes required for viral replication in normal cells [ 457 , 468 ].…”

Section: Manipulating the Tme Using Therapeutic Nucleic Acidsmentioning

confidence: 99%

“…Nowadays, a large repertoire of oncolytic viruses is available and oncolytic virotherapy has been intensively investigated in numerous preclinical and clinical studies, also in combination with other cancer therapies like chemotherapy, radiation therapy, or other immunotherapies [ 456 , 457 , 458 , 459 , 460 , 469 , 470 ]. Table 2 displays approved oncolytic virotherapies and those that have been or are currently tested in clinical trials.…”

Section: Manipulating the Tme Using Therapeutic Nucleic Acidsmentioning

confidence: 99%

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Nucleic Acid-Based Approaches for Tumor Therapy

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Within the last decade, the introduction of checkpoint inhibitors proposed to boost the patients’ anti-tumor immune response has proven the efficacy of immunotherapeutic approaches for tumor therapy. Furthermore, especially in the context of the development of biocompatible, cell type targeting nano-carriers, nucleic acid-based drugs aimed to initiate and to enhance anti-tumor responses have come of age. This review intends to provide a comprehensive overview of the current state of the therapeutic use of nucleic acids for cancer treatment on various levels, comprising (i) mRNA and DNA-based vaccines to be expressed by antigen presenting cells evoking sustained anti-tumor T cell responses, (ii) molecular adjuvants, (iii) strategies to inhibit/reprogram tumor-induced regulatory immune cells e.g., by RNA interference (RNAi), (iv) genetically tailored T cells and natural killer cells to directly recognize tumor antigens, and (v) killing of tumor cells, and reprograming of constituents of the tumor microenvironment by gene transfer and RNAi. Aside from further improvements of individual nucleic acid-based drugs, the major perspective for successful cancer therapy will be combination treatments employing conventional regimens as well as immunotherapeutics like checkpoint inhibitors and nucleic acid-based drugs, each acting on several levels to adequately counter-act tumor immune evasion.

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Combining of Oncolytic Virotherapy and Other Immunotherapeutic Approaches in Cancer: A Powerful Functionalization Tactic

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to direct lysis of these cells. [4] In addition, oncolytic viruses can stimulate immune responses. The most studied oncolytic viruses are Newcastle disease viruses, herpes viruses, coxsackievirus, measles viruses, adenoviruses, polioviruses, poxviruses, and reoviruses. [5,6] Therefore, oncolytic viruses can be a moral treatment option in cancer therapy. The unique feature of oncolytic viruses is that they act selectively and remove tumor cells without damaging non-cancerous cells. [7] Initially, oncolytic virotherapy was studied as monotherapy with unsatisfactory therapeutic effectiveness. Several mechanisms, including the immunosuppressive tumor microenvironment (TME), the off-target sequestration and replication, the existence of neutralizing antibodies, and the balance between viral replication and induced immune response, contribute to oncolytic virotherapy monotherapy resistance. [8] Therefore, researchers have used various combination therapies to overcome these barriers using oncolytic viruses and immunotherapy.Cancer immunotherapy, including methods such as adoptive T cell therapy, immune checkpoint blockade, and monoclonal or bispecific antibodies, has recently succeeded in treating cancer and other immune-related diseases such as autoimmunity. [9][10][11] Oncolytic viruses have found a good place in the treatment of cancer. Administering oncolytic viruses directly or by applying genetic changes can be effective in cancer treatment through the lysis of tumor cells and, in some cases, by inducing immune system responses. Moreover, oncolytic viruses induce antitumor immune responses via releasing tumor antigens in the tumor microenvironment (TME) and affect tumor cell growth and metabolism. Despite the success of virotherapy in cancer therapies, there are several challenges and limitations, such as immunosuppressive TME, lack of effective penetration into tumor tissue, low efficiency in hypoxia, antiviral immune responses, and off-targeting. Evidence suggests that oncolytic viruses combined with cancer immunotherapy-based methods such as immune checkpoint inhibitors and adoptive cell therapies can effectively overcome these challenges. This review summarizes the latest data on the use of oncolytic viruses for the treatment of cancer and the challenges of this method. Additionally, the effectiveness of mono, dual, and triple therapies using oncolytic viruses and other anticancer agents has been discussed based on the latest findings.

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Development of oncolytic virotherapy: from genetic modification to combination therapy

Cited by 40 publications

References 231 publications

Materials promoting viral gene delivery

Materials promoting viral gene delivery

Nucleic Acid-Based Approaches for Tumor Therapy

Combining of Oncolytic Virotherapy and Other Immunotherapeutic Approaches in Cancer: A Powerful Functionalization Tactic

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