A Kunjin replicon vector encoding granulocyte macrophage colony-stimulating factor for intra-tumoral gene therapy

2018

BTT

Oncolytic viruses have demonstrated selective replication and killing of tumor cells. Different types of oncolytic viruses – adenoviruses, alphaviruses, herpes simplex viruses, Newcastle disease viruses, rhabdoviruses, Coxsackie viruses, and vaccinia viruses – have been applied as either naturally occurring or engineered vectors. Numerous studies in animal-tumor models have demonstrated substantial tumor regression and prolonged survival rates. Moreover, clinical trials have confirmed good safety profiles and therapeutic efficacy for oncolytic viruses. Most encouragingly, the first cancer gene-therapy drug – Gendicine, based on oncolytic adenovirus type 5 – was approved in China. Likewise, a second-generation oncolytic herpes simplex virus-based drug for the treatment of melanoma has been registered in the US and Europe as talimogene laherparepvec.

Section: Examples Of Therapeutic Applications Of Oncolytic Virusesmentioning

confidence: 95%

New frontiers in oncolytic viruses: optimizing and selecting for virus strains with improved efficacy

2018

BTT

“…In the context of flaviviruses, the granulocyte macrophage colony-stimulating factor (GM-CSF) expressed from a Kunjin virus vector was subjected to intratumoral administration in mice with subcutaneous CT26 colon carcinoma [ 62 ]. The treatment resulted in a cure of more than 50% of injected mice; tumors were undetectable 18 days after Kunjin-GM-CSF administration.…”

Section: Viral Vectorsmentioning

confidence: 99%

Viral Vectors in Gene Therapy

2018

Diseases

372

244

Applications of viral vectors have found an encouraging new beginning in gene therapy in recent years. Significant improvements in vector engineering, delivery, and safety have placed viral vector-based therapy at the forefront of modern medicine. Viral vectors have been employed for the treatment of various diseases such as metabolic, cardiovascular, muscular, hematologic, ophthalmologic, and infectious diseases and different types of cancer. Recent development in the area of immunotherapy has provided both preventive and therapeutic approaches. Furthermore, gene silencing generating a reversible effect has become an interesting alternative, and is well-suited for delivery by viral vectors. A number of preclinical studies have demonstrated therapeutic and prophylactic efficacy in animal models and furthermore in clinical trials. Several viral vector-based drugs have also been globally approved.

“…Related to cancer immunotherapy, a large number of studies have confirmed that self-amplifying RNA viruses can generate tumor regression, prolonged survival and even tumor protection in animal models for various cancers [ 8 ]. For instance, expression of GM-CSF from Kunjin virus particles resulted in tumor regression in a mouse melanoma model [ 93 ]. Moreover, VEE particles expressing PSCA (prostate stem cell antigen) demonstrated tumor protection in a prostate cancer model [ 94 ].…”

Section: Rna Stability Improvementsmentioning

confidence: 99%

Latest Development on RNA-Based Drugs and Vaccines

2018

Future Sci. OA

Drugs and vaccines based on mRNA and RNA viruses show great potential and direct translation in the cytoplasm eliminates chromosomal integration. Limitations are associated with delivery and stability issues related to RNA degradation. Clinical trials on RNA-based drugs have been conducted in various disease areas. Likewise, RNA-based vaccines for viral infections and various cancers have been subjected to preclinical and clinical studies. RNA delivery and stability improvements include RNA structure modifications, targeting dendritic cells and employing self-amplifying RNA. Single-stranded RNA viruses possess self-amplifying RNA, which can provide extreme RNA replication in the cytoplasm to support RNA-based drug and vaccine development. Although oligonucleotide-based approaches have demonstrated potential, the focus here is on mRNA- and RNA virus-based methods.