Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Using viral vectors to deliver local immunotherapy to glioblastoma.

ABSTRACT: The treatment for glioblastoma (GBM) has not seen significant improvement in over a decade. Immunotherapies target the immune system against tumor cells and have seen success in various cancer types. However, the efficacy of immunotherapies in GBM thus far has been limited. Systemic immunotherapies also carry with them concerns surrounding systemic toxicities as well as penetration of the blood-brain barrier. These concerns may potentially limit their efficacy in GBM and preclude the use of combinatorial immunotherapy, which may be needed to overcome the severe multidimensional immune suppression seen in GBM patients. The use of viral vectors to deliver immunotherapies directly to tumor cells has the potential to improve immunotherapy delivery to the CNS, reduce systemic toxicities, and increase treatment efficacy. Indeed, preclinical studies investigating the delivery of immunomodulators to GBM using viral vectors have demonstrated significant promise. In this review, the authors discuss previous studies investigating the delivery of local immunotherapy using viral vectors. They also discuss the future of these treatments, including the reasoning behind immunomodulator and vector selection, patient safety, personalized therapies, and the need for combinatorial treatment.

SUBMITTER: Haddad AF

PROVIDER: S-EPMC8011938 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Vectors for Glioblastoma Gene Therapy: Viral & Non-Viral Delivery Strategies.

Project description:Glioblastoma multiforme is the most common and aggressive primary brain tumor. Even with aggressive treatment including surgical resection, radiation, and chemotherapy, patient outcomes remain poor, with five-year survival rates at only 10%. Barriers to treatment include inefficient drug delivery across the blood brain barrier and development of drug resistance. Because gliomas occur due to sequential acquisition of genetic alterations, gene therapy represents a promising alternative to overcome limitations of conventional therapy. Gene or nucleic acid carriers must be used to deliver these therapies successfully into tumor tissue and have been extensively studied. Viral vectors have been evaluated in clinical trials for glioblastoma gene therapy but have not achieved FDA approval due to issues with viral delivery, inefficient tumor penetration, and limited efficacy. Non-viral vectors have been explored for delivery of glioma gene therapy and have shown promise as gene vectors for glioma treatment in preclinical studies and a few non-polymeric vectors have entered clinical trials. In this review, delivery systems including viral, non-polymeric, and polymeric vectors that have been used in glioblastoma multiforme (GBM) gene therapy are discussed. Additionally, advances in glioblastoma gene therapy using viral and non-polymeric vectors in clinical trials and emerging polymeric vectors for glioma gene therapy are discussed.

| S-EPMC6359729 | biostudies-literature

Adhesive thermosensitive gels for local delivery of viral vectors.

Project description:Local delivery of viral vectors can enhance the efficacy of therapies by selectively affecting necessary tissues and reducing the required vector dose. Pluronic F127 is a thermosensitive polymer that undergoes a solution-gelation (sol-gel) transition as temperature increases and can deliver vectors without damaging them. While pluronics can be spread over large areas, such as the surface of an organ, before gelation, they lack sufficient adhesivity to remain attached to some tissues, such as the surface of the heart or mucosal surfaces. Here, we utilized blends of pluronic F127 and polycarbophil (PCB), a mucoadhesive agent, to provide the necessary adhesivity for local delivery of viral vectors to the cardiac muscle. The effects of PCB concentration on adhesive properties, sol-gel temperature transition and cytocompatibility were evaluated. Rheological studies showed that PCB decreased the sol-gel transition temperature at concentrations >1% and increased the adhesive properties of the gel. Furthermore, these gels were able to deliver viral vectors and transduce cells in vitro and in vivo in a neonatal mouse apical resection model. These gels could be a useful platform for delivering viral vectors over the surface of organs where increased adhesivity is required.

| S-EPMC7001463 | biostudies-literature

Viral Vectors as Gene Therapy Agents for Treatment of Glioblastoma.

Project description:In this review, we scrutinize the idea of using viral vectors either as cytotoxic agents or gene delivery tools for treatment of glioblastoma multiforme (GBM) in light of the experience that our laboratory has accumulated over ~20 years when using similar vectors in experimental neuroscience. We review molecular strategies and current clinical trials and argue that approaches which are based on targeting a specific biochemical pathway or a characteristic mutation are inherently prone to failure because of the high genomic instability and clonal selection characteristics of GBM. For the same reasons, attempts to develop a viral system which selectively transduces only GBM cells are also unlikely to be universally successful. One of the common gene therapy approaches is to use cytotoxic viruses which replicate and cause preferential lysis of the GBM cells. This strategy, in addition to its reliance on the specific biochemical makeup of the GBM cells, bears a risk of necrotic cell death accompanied by release of large quantities of pro-inflammatory molecules. On the other hand, engaging the immune system in the anti-GBM response seems to be a potential avenue to explore further. We suggest that a plausible strategy is to focus on viral vectors which efficiently transduce brain cells via a non-selective, ubiquitous mechanism and which target (ideally irreversibly) processes that are critical only for dividing tumor cells and are dispensable for quiescent brain cells.

| S-EPMC7764372 | biostudies-literature

Personalized Cancer Vaccines Go Viral: Viral Vectors in the Era of Personalized Immunotherapy of Cancer.

Project description:The aim of personalized cancer vaccines is to elicit potent and tumor-specific immune responses against neoantigens specific to each patient and to establish durable immunity, while minimizing the adverse events. Over recent years, there has been a renewed interest in personalized cancer vaccines, primarily due to the advancement of innovative technologies for the identification of neoantigens and novel vaccine delivery platforms. Here, we review the emerging field of personalized cancer vaccination, with a focus on the use of viral vectors as a vaccine platform. The recent advancements in viral vector technology have led to the development of efficient production processes, positioning personalized viral vaccines as one of the preferred technologies. Many clinical trials have shown the feasibility, safety, immunogenicity and, more recently, preliminary evidence of the anti-tumor activity of personalized vaccination, fostering active research in the field, including further clinical trials for different tumor types and in different clinical settings.

| S-EPMC10706435 | biostudies-literature

VESPER: global and local cryo-EM map alignment using local density vectors.

Project description:An increasing number of density maps of biological macromolecules have been determined by cryo-electron microscopy (cryo-EM) and stored in the public database, EMDB. To interpret the structural information contained in EM density maps, alignment of maps is an essential step for structure modeling, comparison of maps, and for database search. Here, we developed VESPER, which captures the similarity of underlying molecular structures embedded in density maps by taking local gradient directions into consideration. Compared to existing methods, VESPER achieved substantially more accurate global and local alignment of maps as well as database retrieval.

| S-EPMC8027200 | biostudies-literature

Reprogramming systemic and local immune function to empower immunotherapy against glioblastoma.

Project description:The limited benefits of immunotherapy against glioblastoma (GBM) is closely related to the paucity of T cells in brain tumor bed. Both systemic and local immunosuppression contribute to the deficiency of tumor-infiltrating T cells. However, the current studies focus heavily on the local immunosuppressive tumor microenvironment but not on the co-existence of systemic immunosuppression. Here, we develop a nanostructure named Nano-reshaper to co-encapsulate lymphopenia alleviating agent cannabidiol and lymphocyte recruiting cytokine LIGHT. The results show that Nano-reshaper increases the number of systemic T cells and improves local T-cell recruitment condition, thus greatly increasing T-cell infiltration. When combined with immune checkpoint inhibitor, this therapeutic modality achieves 83.3% long-term survivors without recurrence in GBM models in male mice. Collectively, this work unveils that simultaneous reprogramming of systemic and local immune function is critical for T-cell based immunotherapy and provides a clinically translatable option for combating brain tumors.

| S-EPMC9880004 | biostudies-literature

Evolving lessons on nanomaterial-coated viral vectors for local and systemic gene therapy.

Project description:Viral vectors are promising gene carriers for cancer therapy. However, virus-mediated gene therapies have demonstrated insufficient therapeutic efficacy in clinical trials due to rapid dissemination to nontarget tissues and to the immunogenicity of viral vectors, resulting in poor retention at the disease locus and induction of adverse inflammatory responses in patients. Further, the limited tropism of viral vectors prevents efficient gene delivery to target tissues. In this regard, modification of the viral surface with nanomaterials is a promising strategy to augment vector accumulation at the target tissue, circumvent the host immune response, and avoid nonspecific interactions with the reticuloendothelial system or serum complement. In the present review, we discuss various chemical modification strategies to enhance the therapeutic efficacy of viral vectors delivered either locally or systemically. We conclude by highlighting the salient features of various nanomaterial-coated viral vectors and their prospects and directions for future research.

| S-EPMC5561791 | biostudies-other

Sindbis viral vectors transiently deliver tumor-associated antigens to lymph nodes and elicit diversified antitumor CD8+ T-cell immunity.

Project description:Tumors are theoretically capable of eliciting an antitumor immune response, but are often poorly immunogenic. Oncolytic viruses (OVs) have recently emerged as a promising strategy for the immunogenic delivery of tumor-associated antigens (TAAs) to cancer patients. However, safe and effective OV/TAA therapies have not yet been established. We have previously demonstrated that vectors based on Sindbis virus (SV) can inhibit tumor growth and activate the innate immune system in mice. Here, we demonstrate that SV vectors carrying a TAA generate a dramatically enhanced therapeutic effect in mice bearing subcutaneous, intraperitoneal, and lung cancers. Notably, SV/TAA efficacy was not dependent on tumor cell targeting, but was characterized by the transient expression of TAAs in lymph nodes draining the injection site. Early T-cell activation at this site was followed by a robust influx of NKG2D expressing antigen-specific cytotoxic CD8+ T cells into the tumor site, subsequently leading to the generation of long-lasting memory T cells which conferred protection against rechallenge with TAA-positive as well as TAA-negative tumor cells. By combining in vivo imaging, flow cytometry, cytotoxicity/cytokine assays, and tetramer analysis, we investigated the relationship between these events and propose a model for CD8+ T-cell activation during SV/TAA therapy.

| S-EPMC3978799 | biostudies-literature

Perinatal systemic gene delivery using adeno-associated viral vectors.

Project description:Neurodegenerative monogenic diseases often affect tissues and organs beyond the nervous system. An effective treatment would require a systemic approach. The intravenous administration of novel therapies is ideal but is hampered by the inability of such drugs to cross the blood-brain barrier (BBB) and precludes efficacy in the central nervous system. A number of these early lethal intractable diseases also present devastating irreversible pathology at birth or soon after. Therefore, any therapy would ideally be administered during the perinatal period to prevent, stop, or ameliorate disease progression. The concept of perinatal gene therapy has moved a step further toward being a feasible approach to treating such disorders. This has primarily been driven by the recent discoveries that particular serotypes of adeno-associated virus (AAV) gene delivery vectors have the ability to cross the BBB following intravenous administration. Furthermore, safety has been demonstrated after perinatal administration mice and non-human primates. This review focuses on the progress made in using AAV to achieve systemic transduction and what this means for developing perinatal gene therapy for early lethal neurodegenerative diseases.

| S-EPMC4231876 | biostudies-literature

Axonal and subcellular labelling using modified rabies viral vectors.

Project description:An important aspect of any neural circuit is the placement of its output synapses, at levels ranging from macroscopic to subcellular. The many new molecular tools for locating and manipulating synapses are limited by the viral vectors available for delivering them. Adeno-associated viruses are the best current means of labelling and manipulating axons and synapses, but they have never expressed more than one transgene highly enough to label fine axonal structure while also labelling or perturbing synapses. Their slow expression also makes them incompatible with retrograde and transsynaptic vectors, preventing powerful combinatorial experiments. Here we show that deletion-mutant rabies virus can be specifically targeted to cells local to an injection site, brightly labelling axons even when coexpressing two other transgenes. We demonstrate several novel capabilities: simultaneously labelling axons and presynaptic terminals, labelling both dendrites and postsynaptic densities, and simultaneously labelling a region's inputs and outputs using co-injected vectors.

| S-EPMC5939574 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data