Expanded specific T cells to hypomutated regions of the SARS-CoV-2 using mRNA electroporated antigen-presenting cells.

The COVID-19 pandemic has caused about seven million deaths worldwide. Preventative vaccines have been developed including Spike gp mRNA-based vaccines that provide protection to immunocompetent patients. However, patients with primary immunodeficiencies, patients with cancer, or hematopoietic stem cell transplant recipients are not able to mount robust immune responses against current vaccine approaches.

Effects of immune checkpoint blockade on antigen-specific CD8 T cells for use in adoptive cellular therapy.

Adoptive T-cell therapies have been successfully used as prophylaxis or treatment for immunocompromised patients at risk of viral infections or advanced cancers. Unfortunately, for some refractory cancers, they have failed. To overcome this, checkpoint inhibitors are used to rescue immune antitumor responses.

The current landscape of immunotherapy for pediatric brain tumors.

Pediatric central nervous system tumors are the most common solid malignancies in childhood, and aggressive therapy often leads to long-term sequelae in survivors, making these tumors challenging to treat. Immunotherapy has revolutionized prospects for many cancer types in adults, but the intrinsic complexity of treating pediatric patients and the scarcity of clinical studies of children to inform effective approaches have hampered the development of effective immunotherapies in pediatric settings. Here, we review recent advances and ongoing challenges in pediatric brain cancer immunotherapy, as well as considerations for efficient clinical translation of efficacious immunotherapies into pediatric settings.

Exosome/microvesicle content is altered in leucine-rich repeat kinase 2 mutant induced pluripotent stem cell-derived neural cells.

Extracellular vesicles, including exosomes/microvesicles (EMVs), have been described as sensitive biomarkers that represent disease states and response to therapies. In light of recent reports of disease-mirroring EMV molecular signatures, the present study profiled two EMVs from different Parkinson's disease (PD) tissue sources: (a) neural progenitor cells derived from an endogenous adult stem/progenitor cell, called adult human neural progenitor (AHNP) cells, that we found to be pathological when isolated from postmortem PD patients' substantia nigra; and (b) leucine-rich repeat kinase 2 (LRRK2) gene identified patient induced pluripotent stem cells (iPSCs), which were used to isolate EMVs and begin to characterize their cargoes. Initial characterization of EMVs derived from idiopathic patients (AHNPs) and mutant LRRK2 patients showed differences between both phenotypes and when compared with a sibling control in EMV size and release based on Nanosight analysis.

Hypoxia inducible factor-1α (HIF-1α) is required for neural stem cell maintenance and vascular stability in the adult mouse SVZ.

HIF-1α is a hypoxia-inducible protein that regulates many cell and molecular processes, including those involved in angiogenesis and stem cell maintenance. Prior studies demonstrated constitutive HIF-1α stabilization in neural stem cells (NSCs) of the adult mouse SVZ, but its role there has not been elucidated. Here, we tested the hypothesis that HIF-1α plays an essential role in the maintenance of adult NSCs and stabilization of the SVZ vascular niche using conditional, tamoxifen-inducible Hif1a knock-out mice.

The role of extracellular vesicles in the progression of neurodegenerative disease and cancer.

Extracellular vesicles (EVs) are released from many cell types, including normal and pathological cells, and range from 30 to 1000 nm in size. Once thought to be a mechanism for discarding unwanted cellular material, EVs are now thought to play a role in intercellular communication. Evidence is accruing that EVs are capable of carrying mRNAs, miRNAs, noncoding RNAs, and proteins, including those associated with neurodegenerative diseases and cancer, which may be exchanged between cells.

Regenerative medicine in Alzheimer's disease.

Identifying novel, effective therapeutics for Alzheimer's disease (AD) is one of the major unmet medical needs for the coming decade. Because the current paradigm for developing and testing disease-modifying AD therapies is protracted and likely to be even longer, with the shift toward earlier intervention in preclinical AD, it is an open issue whether we can develop, test, and widely deploy a novel therapy in time to help the current at-risk generation if we continue to follow the standard paradigms of discovery and drug development. There is an imperative need to find safe and effective preventive measures that can be distributed rapidly to stem the coming wave of AD that will potentially engulf the next generation.

Neural stem/progenitor cells display a low requirement for oxidative metabolism independent of hypoxia inducible factor-1alpha expression.

Neural stem/progenitor cells (NSPCs) are multipotent cells within the embryonic and adult brain that give rise to both neuronal and glial cell lineages. Maintenance of NSPC multipotency is promoted by low oxygen tension, although the metabolic underpinnings of this trait have not been described. In this study, we investigated the metabolic state of undifferentiated NSPCs in culture, and tested their relative reliance on oxidative versus glycolytic metabolism for survival, as well as their dependence on hypoxia inducible factor-1alpha (HIF-1α) expression for maintenance of metabolic phenotype.