A5104108323- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Nanowire Synthesis and Applications
- Advancements in Semiconductor Devices and Circuit Design
- T-cell and B-cell Immunology
- Biotechnology and Related Fields
- Genomics, phytochemicals, and oxidative stress
- Immune cells in cancer
- Immunotherapy and Immune Responses
Medical University of Vienna
2020-2024
The metabolic state represents a major hurdle for an effective adoptive T cell therapy (ACT). Indeed, specific lipids can harm CD8+ (CTL) mitochondrial integrity, leading to defective antitumor responses. However, the extent which affect CTL functions and fate remains unexplored. Here, we show that linoleic acid (LA) is positive regulator of activity by improving fitness, preventing exhaustion, stimulating memory-like phenotype with superior effector functions. We report LA treatment...
T cells engineered to express chimeric antigen receptors (CAR-T cells) have shown impressive clinical efficacy in the treatment of B cell malignancies. However, development CAR-T therapies for solid tumors is hampered by lack truly tumor-specific antigens and poor control over activity. Here we present an avidity-controlled CAR (AvidCAR) platform with inducible logic functions. The key combination (i) improved design which enables controlled dimerization (ii) a significant reduction...
Current US Food and Drug Administration-approved chimeric antigen receptor (CAR) T cells harbor the cell (TCR)-derived ζ chain as an intracellular activation domain in addition to costimulatory domains. The functionality a CAR format of other chains TCR complex, namely CD3δ, CD3ε CD3γ, instead ζ, remains unknown. In present study, we have systematically engineered new CD3 CARs, each containing only one We found that CARs or CD3γ cytoplasmic tails outperformed conventional vivo....
ABSTRACT T-cell antigen receptors (TCRs) exhibit inherent cross-reactivity which broadens the spectrum of epitopes that are recognizable by a finite TCR-repertoire but also carries risk autoimmunity. However, TCRs support high level specificity as they allow T-cells to discriminate single antigenic peptide/MHC complexes (pMHCs) against millions structurally related self-pMHCs, in some cases based on absence or presence methyl-group. How manage convey such seemingly contrary properties and...
Low antigen sensitivity and a gradual loss of effector functions limit the clinical applicability chimeric receptor (CAR)–modified T cells call for alternative designs effective cell–based cancer immunotherapy. Here, we applied advanced microscopy to demonstrate that TCR/CD3-based synthetic constructs (TCC) outperform second-generation CAR formats with regard conveyed sensitivities by up thousandfold. TCC-based recognition occurred without adverse nonspecific signaling, which is typically...
Se puede pensar en la biología sintética como un factor de cambio que juega papel central convergencia NBIC, o BINC, contemporánea. Es decir, las nanociencias, biociencias, ciencias información y cognitivas. Aunque mayoría los biólogos sintéticos aún no se han dado cuenta, su campo apela a nuestra imaginación al marcarse metas hasta ahora asociaban con ciencia premoderna alquimia. En este artículo desarrollaran algunas características sintética, así el impacto ésta noción tradicional...
ABSTRACT Low antigen sensitivity and a gradual loss of effector functions limit the clinical applicability chimeric receptor (CAR)-modified T-cells call for alternative designs effective T-cell-based cancer immunotherapy. Here we applied advanced microscopy to demonstrate that TCR/CD3-based synthetic constructs (TCC) outperform second-generation CAR formats with regard conveyed sensitivities by up thousand-fold. TCC-based recognition occurred without adverse non-specific signaling, which is...
Abstract Current FDA-approved CAR T cells harbour the TCR-derived ζ chain as intracellular activation domain. The contribution of other chains TCR complex, namely CD3δ, CD3ε, and CD3γ in a format remains unknown. Here, we have systematically engineered novel CD3-based CARs. Unexpectedly, CARs containing CD3ε or cytoplasmic tails outperformed conventional vivo . Transcriptomic proteomic analysis revealed differences potential, metabolism stimulation-induced cell dysfunctionality that...