The recent clinical success of cancer immunotherapy with checkpoint blockade has led to renewed interest into the development of immune modulatory agents with the capacity to activate anti-tumor T cell responses. Standardization of optimized in vitro assays for efficient assessment of immune function of such new drugs is thus needed to facilitate clinical development of the optimal drug candidates. Here, we describe an optimized version of T cell suppression assay designed to test the effect of immunomodulatory agents on T cell function and activation. We apply this assay to investigate the agonist activity of the T cell co-stimulatory molecule glucocorticoid-induced TNFR-related protein (GITR). We detail a protocol for concurrent assessment of multiple levels of T cell functional modulation upon GITR engagement, including T cell priming, activation and effector function, in a single assay. As human GITR agonist antibodies are currently under development, availability of standardized cell-based functional assays of GITR agonism is instrumental to translate anti-GITR therapy into the clinical setting.
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http://dx.doi.org/10.1016/bs.mie.2019.08.012 | DOI Listing |
Alzheimers Dement
December 2024
University of Florida / Center for Translational Research in Neurodegenerative Disease, Gainesville, FL, USA.
Background: Vaxxinity is developing an active immunotherapy targeting Tau for Alzheimer's disease (AD) and other tauopathies. VXX-301 is a multi-epitope vaccine designed to target the N-terminal and repeat domains of Tau. This design enables targeting multiple forms of Tau thought to contribute to Tau associated pathologies.
View Article and Find Full Text PDFBackground: Alzheimer's Disease (AD) is the leading form of senile dementia, affecting ∼6 million Americans and having a national economic impact of $321 billion, numbers expected to double by 2050. The major pathological hallmarks of AD include Amyloid Beta (Aβ) plaques and Tau neurofibrillary tangles (NFT). The first goal of this research was to develop novel forms of carbon dots (CD) using various precursors.
View Article and Find Full Text PDFBackground: DYRK1A overexpression, common in neurodegenerative diseases like Alzheimer's (AD), contributes to neurofibrillary tangles via Tau protein hyperphosphorylation and amyloid plaque formation, key AD hallmarks. Therefore, DYRK1A has been regarded as a novel target for neurodegenerative diseases. However, developing DYRK1A selective inhibitors has been a difficult challenge due to the highly conserved ATP-binding site of protein kinases, particularly among the CMGC family.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Yonsei University, Incheon, Incheon, Korea, Republic of (South).
Background: Cyclin Y (CCNY) is a member of cyclin protein family inhibiting long-term synaptic plasticity, which is related to the learning and memory function in neuronal system. Recently, CCNY has been reported to associate with the cognitive deficits in Alzheimer's disease (AD).
Method: In this study, we discovered PFTAIRE peptide to diminish CCNY protein level and to ameliorate cognitive dysfunction in AD.
Background: Progranulin (GRN) plays a critical role in familial frontotemporal dementia (fFTD), where GRN haploinsufficiency leads to reduction in PGRN levels in the brain, resulting in degeneration of neurons in the frontal lobe of brain responsible for personality, language, and behavior. FTD is the most common dementia in people under 60. Sortilin (Sort1), expressed by neurons, endocytoses, and delivers PGRN rapidly to lysosomes for degradation.
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