Effect of Serial Systemic and Intratumoral Injections of Oncolytic ZIKVBR in Mice Bearing Embryonal CNS Tumors

Ferreira, Raiane O.; Granha, Isabela; Ferreira, Rodolfo Sanches; Bueno, Heloisa de Siqueira; Okamoto, Oswaldo Keith; Kaid, Carolini; Zatz, Mayana

doi:10.3390/v13102103

Cited by 10 publications

(11 citation statements)

References 26 publications

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“…Several groups used tumor organoids to evaluate the efficacy of oncolytic virus therapy in preclinical settings. These studies demonstrated that oncolytic adenovirus could show selective replication in PDTOs while not in organoids derived from normal tissue, and tumor organoids are ideal preclinical models to predict responses to oncolytic adenovirus therapy ( 76 – 78 ). However, these studies failed to investigate oncolytic virus therapy in complex immune–organoids.…”

Section: Complex Organoids and Immunotherapeuticsmentioning

confidence: 99%

Patient-Derived Tumor Organoids: New Progress and Opportunities to Facilitate Precision Cancer Immunotherapy

et al. 2022

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Cancer immunotherapy has revolutionized the field of cancer treatment in recent years. However, not all patients receiving cancer immunotherapy exhibit durable responses, and reliable, high-throughput testing platforms are urgently needed to guide personalized cancer immunotherapy. The ability of patient-derived tumor organoids to recapitulate pivotal features of original cancer tissues makes them useful as a preclinical model for cancer research and precision medicine. Nevertheless, many challenges exist in the translation of tumor organoid research to clinical decision making. Herein we discuss the applications of patient-derived tumor organoid models and the advances and potential of using complex immune-organoid systems as testing platforms to facilitate precision cancer immunotherapy. In addition, we highlight intriguing applications of tumor organoids with novel multi-omics in preclinical cancer research, highlighting genetic editing, proteomics, and liquid biopsy.

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Section: Complex Organoids and Immunotherapeuticsmentioning

confidence: 99%

Patient-Derived Tumor Organoids: New Progress and Opportunities to Facilitate Precision Cancer Immunotherapy

et al. 2022

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“…Furthermore, ZIKV-mediated tumor clearance provided a durable protection against syngeneic tumor rechallenges. The Brazilian ZIKV BR strain has also been evaluated for its oncolytic activity against embryonal CNS tumors [ 44 ]. The investigation of different administration routes and the number of injections of ZIKV BR on tumor tropism, tumor eradication, and side effects demonstrated a tropism to the brain after systemic delivery in mice with subcutaneous tumors.…”

Section: Preclinical Studies Using Oncolytic Self-replicating Rna Vir...mentioning

confidence: 99%

“…The investigation of different administration routes and the number of injections of ZIKV BR on tumor tropism, tumor eradication, and side effects demonstrated a tropism to the brain after systemic delivery in mice with subcutaneous tumors. In the case of brain tumors, systemic administration of ZIKV BR resulted in efficient tumor eradication and increased survival without any neurological or other organ injury [ 44 ]. In another study, the safety and therapeutic activity of the intrathecal administration of ZIKVBR were evaluated in three dogs with spontaneous advanced stage brain tumors [ 45 ].…”

Section: Preclinical Studies Using Oncolytic Self-replicating Rna Vir...mentioning

confidence: 99%

Therapeutic Applications for Oncolytic Self-Replicating RNA Viruses

Lundström¹

2022

IJMS

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Self-replicating RNA viruses have become attractive delivery vehicles for therapeutic applications. They are easy to handle, can be rapidly produced in large quantities, and can be delivered as recombinant viral particles, naked or nanoparticle-encapsulated RNA, or plasmid DNA-based vectors. The self-replication of RNA in infected host cells provides the means for generating much higher transgene expression levels and the possibility to apply substantially reduced amounts of RNA to achieve similar expression levels or immune responses compared to conventional synthetic mRNA. Alphaviruses and flaviviruses, possessing a single-stranded RNA genome of positive polarity, as well as measles viruses and rhabdoviruses with a negative-stranded RNA genome, have frequently been utilized for therapeutic applications. Both naturally and engineered oncolytic self-replicating RNA viruses providing specific replication in tumor cells have been evaluated for cancer therapy. Therapeutic efficacy has been demonstrated in animal models. Furthermore, the safe application of oncolytic viruses has been confirmed in clinical trials. Multiple myeloma patients treated with an oncolytic measles virus (MV-NIS) resulted in increased T-cell responses against the measles virus and several tumor-associated antigen responses and complete remission in one patient. Furthermore, MV-CEA administration to patients with ovarian cancer resulted in a stable disease and more than doubled the median overall survival.

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“…Another group studied ZIKV oncolytic activity in COs co-cultured with CNS tumor cells and were able to showed that ZIKV diminished tumor growth, which was also found in mouse models and other organoid studies [93,112]. Another paper looked at saxitoxin (STX), which is produced by the cyanobacteria, Raphidiopsis raciborskii, and is common in Brazil [78].…”

Section: Unguided Organoid Modelsmentioning

confidence: 99%

Methodologies for Generating Brain Organoids to Model Viral Pathogenesis in the CNS

2021

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(1) Background: The human brain is of interest in viral research because it is often the target of viruses. Neurological infections can result in consequences in the CNS, which can result in death or lifelong sequelae. Organoids modeling the CNS are notable because they are derived from stem cells that differentiate into specific brain cells such as neural progenitors, neurons, astrocytes, and glial cells. Numerous protocols have been developed for the generation of CNS organoids, and our goal was to describe the various CNS organoid models available for viral pathogenesis research to serve as a guide to determine which protocol might be appropriate based on research goal, timeframe, and budget. (2) Methods: Articles for this review were found in Pubmed, Scopus and EMBASE. The search terms used were “brain + organoid” and “CNS + organoid” (3) Results: There are two main methods for organoid generation, and the length of time for organoid generation varied from 28 days to over 2 months. The costs for generating a population of organoids ranged from USD 1000 to 5000. (4) Conclusions: There are numerous methods for generating organoids representing multiple regions of the brain, with several types of modifications for fine-tuning the model to a researcher’s specifications. Organoid models of the CNS can serve as a platform for characterization and mechanistic studies that can reduce or eliminate the use of animals, especially for viruses that only cause disease in the human CNS.

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Effect of Serial Systemic and Intratumoral Injections of Oncolytic ZIKVBR in Mice Bearing Embryonal CNS Tumors

Cited by 10 publications

References 26 publications

Patient-Derived Tumor Organoids: New Progress and Opportunities to Facilitate Precision Cancer Immunotherapy

Patient-Derived Tumor Organoids: New Progress and Opportunities to Facilitate Precision Cancer Immunotherapy

Therapeutic Applications for Oncolytic Self-Replicating RNA Viruses

Methodologies for Generating Brain Organoids to Model Viral Pathogenesis in the CNS

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