Alphaviral-Based Strategies for the Immunotherapy of Cancer

Nelson, Edward L.; Smith, Jonathan

doi:10.1007/978-1-59259-680-5_15

Cited by 4 publications

(13 citation statements)

References 120 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this ex vivo transduction of DCs can result in premature activation and acquisition of the mature phenotype (21)(22)(23), contributing to the difficulties noted in adoptive transfer of DCs. Various issues, including preexisting antivector immunity, the potential for adventitial mRNA splicing, and to a lesser extent genomic integration, complicate the clinical application of immunotherapies based on these DNA virus-derived vectors (24). Alternatively, the use of vectors derived from alphaviruses, positive-strand RNA viruses that have a life cycle entirely restricted to the cytoplasm and have limited antivector immunity, would not be subject to the concerns surrounding the use of DNA virus-derived vectors (24).…”

Section: Introduction T He Appreciation Of Dendritic Cell (Dc) Biologmentioning

confidence: 98%

Restricted and Selective Tropism of a Venezuelan Equine Encephalitis Virus-Derived Replicon Vector for Human Dendritic Cells

et al. 2007

Self Cite

View full text Add to dashboard Cite

Dendritic cells (DCs) consist of heterogeneous phenotypic populations and have diverse immunostimulatory functions dependent on both lineage and functional phenotype, but as exceptionally potent antigen-presenting cells, they are targets for generating effective antigen-specific immune responses. A promising replicon particle vector derived from Venezuelan equine encephalitis virus (VEE) has been reported to transduce murine footpad DCs. However, the receptive DC subset, the degree of restriction for this tropism, and the extent of conservation between rodents and humans have not been well characterized. Using fresh peripheral blood DCs, mononuclear cells, monocyte-derived macrophages, and monocyte-derived DCs, our results demonstrate conservation of VEE replicon particle (VRP) tropism for DCs between humans and rodents. We observed that a subset of immature myeloid DCs is the target population, and that VRP-transduced immature DCs retain intact functional capacity, for example, the ability to resist the cytopathic effects of VRP transduction and the capacity to acquire the mature phenotype. These studies support the demonstration of selective VRP tropism for human DCs and provide further insight into the biology of the VRP vector, its parent virus, and human DCs.

show abstract

Section: Introduction T He Appreciation Of Dendritic Cell (Dc) Biologmentioning

confidence: 98%

Restricted and Selective Tropism of a Venezuelan Equine Encephalitis Virus-Derived Replicon Vector for Human Dendritic Cells

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…The potency of VRP-based immunotherapy is likely due, at least in part, to its DC tropism [30,[32][33][34]. This tropism was first described in murine models [32] and more recently in human systems [33,34].…”

Section: Discussionmentioning

confidence: 97%

“…VRP rapidly coopt cellular protein synthesis to produce extraordinarily large quantities of vector encoded proteins, albeit transiently [31,35]. There is a very low frequency of anti-VEE immunity in humans and it has been shown in pre-clinical models that this vector system can be effectively used for repeated immunizations in the same individual with no loss of vector efficacy [30]. By the nature of these characteristics, the VRP vector system provides an opportunity to directly target, in situ, the most potent antigen presenting and immunostimulatory cell for the production of abundant heterologous protein.…”

Section: Introductionmentioning

confidence: 98%

“…The VRP vector system is a propagation deficient, singlecycle vector system, which importantly, has a natural tropism for dendritic cells (DCs) [32][33][34]. The VRP life cycle is entirely restricted to the cytoplasm [30], thus transport across the nuclear membrane is not required for its functional capacity and chromosomal integration or inappropriate splicing of engineered coding sequences is not a concern. VRP rapidly coopt cellular protein synthesis to produce extraordinarily large quantities of vector encoded proteins, albeit transiently [31,35].…”

Section: Introductionmentioning

confidence: 99%

“…The normal and physiologic expression of neu in the rat species would be expected to recapitulate intrinsic central and peripheral tolerance to self antigens that can also be over-expressed, non-mutated TAAs. The virus-like particle (VRP) vector, derived from the alphavirus Venezuelan equine encephalitis (VEE) virus [30,31] is an attractive immunotherapeutic vector due to several biological characteristics. The VRP vector system is a propagation deficient, singlecycle vector system, which importantly, has a natural tropism for dendritic cells (DCs) [32][33][34].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

VRP immunotherapy targeting neu: treatment efficacy and evidence for immunoediting in a stringent rat mammary tumor model

Laust

Sur

Wang

et al. 2007

Breast Cancer Res Treat

Self Cite

View full text Add to dashboard Cite

The ability to overcome intrinsic tolerance to a strict "self" tumor-associated antigen (TAA) and successfully treat pre-existing tumor is the most stringent test for anti-tumor immunotherapeutic strategies. Although this capacity has been demonstrated in various models using complicated strategies that may not be readily translated into the clinical arena, straightforward antigen-specific immunotherapeutic strategies in the most stringent models of common epithelial cancers have largely failed to meet this standard. We employed an immunotherapeutic strategy using an alphavirus-based, virus-like replicon particle (VRP), which has in vivo tropism for dendritic cells, to elicit immune responses to the non-mutated TAA rat neu in an aggressive rat mammary tumor model. Using this VRP-based immunotherapeutic strategy targeting a single TAA, we generated effective anti-tumor immunity in the setting of pre-existing tumor resulting in the cure of 36% of rats over multiple experiments, P = 0.002. We also observed down-regulation of rat neu expression in tumors that showed initial responses followed by tumor escape with resumption of rapid tumor growth. These responses were accompanied by significant anti-tumor proliferative responses and CD8+ cellular tumor infiltrates, all of which were restricted to animals receiving the anti-neu immunotherapy. Together these data, obtained in a stringent "self" TAA model, indicate that the VRP-based antigen-specific immunotherapy elicits sufficiently potent immune responses to exert immunologic pressure, selection, and editing of the growing tumors, thus supporting the activity of this straightforward immunotherapy and suggesting that it is a promising platform upon which to build even more potent strategies.

show abstract

Polymeric 3D printed structures for soft‐tissue engineering

Stratton

Manoukian

Patel

et al. 2017

J of Applied Polymer Sci

View full text Add to dashboard Cite

Three-dimensional (3D) printing, or rapid prototyping, is a fabrication technique that is used for various engineering applications with advantages such as mass production and fine tuning of spatial-dimensional properties. Recently, this fabrication method has been adopted for tissue engineering applications due to its ability to finely tune porosity and create precise, uniform, and repeatable structures. This review aims to introduce 3D printing applications in soft-tissue engineering and regenerative medicine including state-of-the-art scaffolds and key future challenges. Furthermore, 3D printing of individual cells, an evolution of traditional 3D printing technology which represents a cutting-edge technique for the creation of cell seeded scaffolds in vitro, is discussed. Key advances demonstrate the advantages of 3D printing, while also highlighting potential shortcomings to improve upon. It is clear that as 3D printing technology continues to develop, it will serve as a truly revolutionary means for fabrication of structures and materials for regenerative applications.

show abstract

Alphaviral-Based Strategies for the Immunotherapy of Cancer

Cited by 4 publications

References 120 publications

Restricted and Selective Tropism of a Venezuelan Equine Encephalitis Virus-Derived Replicon Vector for Human Dendritic Cells

Restricted and Selective Tropism of a Venezuelan Equine Encephalitis Virus-Derived Replicon Vector for Human Dendritic Cells

VRP immunotherapy targeting neu: treatment efficacy and evidence for immunoediting in a stringent rat mammary tumor model

Polymeric 3D printed structures for soft‐tissue engineering

Contact Info

Product

Resources

About