A5040574475- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- Transgenic Plants and Applications
- Immune Cell Function and Interaction
- Silicon Carbide Semiconductor Technologies
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- 3D Printing in Biomedical Research
- Viral Infectious Diseases and Gene Expression in Insects
- Nanowire Synthesis and Applications
- Cancer Immunotherapy and Biomarkers
- Advancements in Semiconductor Devices and Circuit Design
- Additive Manufacturing and 3D Printing Technologies
- Interactive and Immersive Displays
The University of Texas MD Anderson Cancer Center
2025
Washington University in St. Louis
2022-2024
National Taiwan University of Science and Technology
2016
While chimeric antigen receptor (CAR) T cells targeting CD19 can cure a subset of patients with B cell malignancies, most treated will not achieve durable remission. Identification the mechanisms leading to failure is essential broadening efficacy this promising platform. Several studies have demonstrated that disruption genes and transcripts lead disease relapse after initial response; however, few other tumor-intrinsic drivers CAR been reported. Here we identify expression Golgi-resident...
Both higher- and lower-affinity self-reactive CD4+ T cells are expanded in autoimmunity; however, their individual contribution to disease remains unclear. We addressed this question using peptide-MHCII chimeric antigen receptor (pMHCII-CAR) specifically deplete peptide-reactive mice. Integration of improvements CAR engineering with TCR repertoire analysis was critical for interrogating vivo the role affinity autoimmunity. Our original MOG35-55 pMHCII-CAR, which targeted only higher-affinity...
Chimeric antigen receptor (CAR)-based therapies have pioneered synthetic cellular immunity but remain limited in their long-term efficacy. Emerging data suggest that dysregulated CAR-driven T-cell activation causes dysfunction and therapeutic failure. To re-engage the precision of endogenous response, we designed MHC-independent receptors (miTCR) by linking antibody variable domains to constant chains. Using predictive modeling, observed this standard "cut paste" approach protein design...
<title>Abstract</title> Nearly all chimeric antigen receptors (CARs) initiate intracellular signaling in the absence of antigen, referred to as “tonic signaling”. Tonic CARs containing CD28 costimulatory domain has been shown drive T cell exhaustion; contrast, we previously found that tonic 41BB-containing enhances function. Using a panel targeting B CD22, identified 41BB activates BACH2, transcriptional regulator directs stem and memory programs. Overexpression BACH2 prevented exhaustion...
Abstract Chimeric antigen receptor (CAR) natural killer (NK) cell immunotherapy offers a promising approach against cancer. However, the molecular mechanisms governing CAR NK activity remain poorly understood. In this study, we identified transcription factor cAMP response element modulator (CREM) as pivotal regulator of function. Using Raji model, single-cell RNA sequencing revealed marked upregulation CREM in cells during peak anti-tumor after adoptive transfer. expression correlated with...
The 3D printing, also called additive manufacturing, is a combination of three-dimensional digital design technology, material science, manufacturing and intelligent control mechatronics system etc. main purpose this study to develop color photo-curable by using multiple Piezoelectric heads. Four different colors (CMYW) curable materials (UV resin) were developed first. This has finished integration mixing, piezo process, CMYW process multi-inkjet head proposed can provide colorful object...
Abstract Chimeric antigen receptor (CAR) engineered T cells often fail to enact effector functions after infusion into patients. Understanding the biological pathways that lead CAR failure is of critical importance in design more effective therapies. We developed and validated an vitro model drives cell dysfunction through chronic activation interrogated how costimulatory domains contribute failure. found dysfunctional CD28-based CARs targeting CD19 bear hallmarks classical exhaustion while...
Abstract Chimeric antigen receptor (CAR)-based therapies have pioneered synthetic cellular immunity against cancer, however remain limited in their scope and long-term efficacy. Emerging data suggest that dysregulated CAR-driven T cell activation causes dysfunction therapeutic failure. To re-engage the endogenous response, we designed hybrid MHC-independent receptors (miTCRs) by linking antibody variable domains to TCR constant domains. While functional, observed stark differences...
<p>Supplementary Figure 6 | a-b, Cytotoxicity of a, miTCR1 and b, miTCR2 variants against Nalm6. c-d, Long-term flow cytometry-based cytotoxicity lead c, d, variants. e, Quantification cytokines in supernatants 24h after co-culture engineered T cells with f, Expression TCRC chains αCD22 miTCR1, CD22 CD19 Jurkat cells. g, Induction reporter NFAT-GFP upon exposure to CD19+CD22+ Nalm6 Screening studies a-b performed using two independent donors; representative data from three one donor....
<p>Supplementary Figure 7 | a, Overlay of predicted mut031 α chain variable region and resolved FMC63 structure. Modeling performed using AlphaFold2. b, Memory lineages human T cells engineered to express miTCR1 WT or mut035 at the conclusion manufacturing cultures. c-d, Proportion that were early lineage (naïve central memory) c, throughout 6 day stimulation cultures d, one after clearance Nalm6. e, Expansion expressing WT, 19/BBζ CAR from two donors. b-d, data donor.</p>
<div>Abstract<p>Chimeric antigen receptor (CAR)–based therapies have pioneered synthetic cellular immunity but remain limited in their long-term efficacy. Emerging data suggest that dysregulated CAR-driven T-cell activation causes dysfunction and therapeutic failure. To re-engage the precision of endogenous response, we designed MHC-independent receptors (miTCR) by linking antibody variable domains to constant chains. Using predictive modeling, observed this standard “cut paste”...
<p>Supplementary Figure 5 | a-b, Expression of TCR constant chains on the surface a, Jurkat and b, human T cells transduced with miTCR variants. c-d, Comparison expression in miTCR1 miTCR2 variant engineered c, Jurkats d, cells. e, Change based presence or absence PD insertion miTCRα chain. f, NFAT g, NFκB reporter expressing 1G4 variants response to Nalm6. h, Expansion upon exposure cumulative data from three independent donors. b,e, representative Screening studies h performed using...
<p>Supplementary Figure 1 | a-b, Expression of NFAT and NFκB in reporter Jurkat cells expressing CARs or miTCRs response to a, CD19+ Nalm6 CD19- Molm14. b, Representative flow cytometry plot TCR constant chain expression after dual TRAC TRBC disruption. c, Summary data surface disruption n=8 individual donors. Analysis using two-sided Student’s t-test.</p>
<p>Supplementary Figure 2 | a-d, Expression of a, TCR constant chains and mCherry transduction marker, b, FMC63 c, d, CD3ε in primary human T cells engineered with CARs or miTCRs. e, Comparison surface expression miTCR1 miTCR2 n=6 independent donors. f, Median fluorescence intensity (MFI) APC on that bound soluble CD19-APC conjugate. Representative five Analysis using Student’s t-test two-way ANOVA.</p>
<p>Supplementary Figure 8 | a, Cytotoxicity, as measured by fold change in Nalm6 growth during co-culture, and b, expansion of human T cells expressing transgenic TCR 1G4, 19/BBζ or 19/28ζ CAR against Nalm6WT Nalm6triple. c-d, Endogenous expression 41BBL, CD80 CD86 c, Raji d, K562 cell lines. e, Growth rate engineered f-g, Cytotoxicity mut035 over time f, acute stimulation g, re-stimulation. were initially co-cultured with re-stimulated Nalm6WT; Nalm641BBL Nalm6WT. h, Percent either...
<p>Supplementary Figure 4 | Names and amino acid changes of miTCR variant panel. PD insertions are highlighted in blue.</p>
<p>Supplementary Figure 3 | a, Predicted structures of miTCR1 and miTCR2 α β chains overlaid on resolved TCR chains. b, Overlay five highest-ranking predictions for variable-constant chain interface. c, Resolved native V-C interface structure predicted WT modified d, WT, chains.</p>