A5052429609- CAR-T cell therapy research
- Peptidase Inhibition and Analysis
- Synthesis and Biological Evaluation
- Myasthenia Gravis and Thymoma
- Virus-based gene therapy research
- Signaling Pathways in Disease
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Nanowire Synthesis and Applications
- Immune Response and Inflammation
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Peripheral Neuropathies and Disorders
- Vector-borne infectious diseases
- Complement system in diseases
- RNA modifications and cancer
- Biosimilars and Bioanalytical Methods
- Genetic Syndromes and Imprinting
- Genomics and Chromatin Dynamics
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Invertebrate Immune Response Mechanisms
- RNA Research and Splicing
- Silicon Carbide Semiconductor Technologies
University of Pennsylvania
2006-2025
Abramson Cancer Center
2016
University of Toronto
1998
Howard Hughes Medical Institute
1998
Mount Sinai Hospital
1998
Medical Council of Canada
1998
Successful tumor eradication by chimeric antigen receptor-expressing (CAR-expressing) T lymphocytes depends on CAR cell persistence and effector function. We hypothesized that CD4+ CD8+ cells may exhibit distinct phenotypes, depending the identity of specific intracellular signaling domains (ICDs) used to generate CAR. First, we demonstrate ICOS ICD dramatically enhanced in vivo CAR-expressing that, turn, increased expressing either CD28- or 4-1BB-based CARs. These data indicate was highly...
Abstract Synthetic receptor signalling has the potential to endow adoptively transferred T cells with new functions that overcome major barriers in treatment of solid tumours, including need for conditioning chemotherapy 1,2 . Here we designed chimeric receptors have an orthogonal IL-2 extracellular domain (ECD) fused intracellular (ICD) common γ-chain (γ c ) cytokines IL-4, IL-7, IL-9 and IL-21 such cytokine elicits corresponding γ signal. Of these, signal through IL-2Rβ-ECD–IL-9R-ICD (o9R)...
A challenge when targeting T-cell lymphoma with chimeric antigen receptor (CAR) therapy is that target antigens are often shared between T cells and tumor cells, resulting in fratricide CAR on-target cytotoxicity on normal cells. CC chemokine 4 (CCR4) highly expressed many mature malignancies, such as adult leukemia/lymphoma (ATLL) cutaneous (CTCL), has a unique expression profile CCR4 predominantly by type-2 type-17 helper (Th2 Th17) regulatory (Treg), but it rarely other (Th) subsets CD8+...
Despite the success of chimeric antigen receptor (CAR) T-cell therapy against hematologic malignancies, successful targeting solid tumors with CAR T cells has been limited by a lack durable responses and reports toxicities. Our understanding therapeutic efficacy in could be improved quantitative tools that allow characterization T-targeted antigens accurate monitoring response.
High-level expression of the human growth hormone (hGH) gene is limited to somatotrope and lactosomatotrope cells anterior pituitary. We previously identified a locus control region (LCR) for hGH composed four tissue-specific DNase I-hypersensitive sites (HS) located between −14.6 kb −32 5′ transcription start site that responsible establishing physiologically regulated chromatin domain transgene in mouse In present study we demonstrated LCR mediates restriction on an otherwise weakly...
Patients can develop human anti mouse immune responses against CD19- specific CAR T cells (CARTs) due to the use of a murine scFv redirect cells. To mitigate immunogenicity, humanization process FMC63- based binder was undertaken that resulted in (119) when introduced into showed improved activity humanized model. further characterize how binding domains affect CART function, we screened yeast display library identify an array fully CD19 binders. We saw significant differences ability CARs...
Abstract Patients can develop human anti-mouse immune responses against CD19-specific chimeric antigen receptor (CAR) T cells due to the use of a murine single-chain variable fragment redirect cells. We screened yeast display library identify an array fully CD19 binders and performed series studies select most promising CAR. observed significant differences in ability CARs employing these be expressed on cell surface, induce tonic signaling, T-cell function, mediate tumor killing, recognize...
Allogeneic stem cell transplantation (allo-SCT) is the only potentially curative option in relapsed or high risk acute myeloid leukemia (AML). However, patients are often excluded due to refractory disease. Chimeric Antigen Receptor (CAR) T therapy has shown significant efficacy lymphoid and its successful translation AML would constitute a vertical advance field. CD33 known be expressed on blasts. We developed 2nd generation CAR from anti-CD33 scFv of Gemtuzumab ozogamicin, 41BB...
The normal accumulation of adult α and β globins in definitive erythrocytes is critically dependent upon processes that ensure the cognate mRNAs are maintained at high levels transcriptionally silent, but translationally active progenitor cells. impact these post-transcriptional regulatory events on expression embryonic ζ globin not known, as its encoding mRNA normally transcribed during erythropoiesis. Recently, though, has been recognized a potential therapeutic for thalassemia sickle-cell...
<h3>Background</h3> Metastatic castration-resistant prostate cancer (mCRPC) represents the lethal phase of advanced and is resistant to most immune therapies, including checkpoint immunotherapy. While chimeric antigen receptor (CAR) T cell therapy a promising approach treat mCRPC, dose-dependent and/or antigen-dependent toxicity validated CAR targets, such as prostate-specific membrane (PSMA), are still challenge. Many antigens expressed on PSMA, also found critical normal tissues,...
Abstract Allogeneic stem cell transplantation is the only option in relapsed acute myeloid leukemia (AML). However, patients are often excluded due to refractory disease. The successful translation of Chimeric Antigen Receptor (CAR) T therapy AML would constitute a vertical advance field. We developed 2nd generation CAR using anti CD33 scFv Gemtuzumab ozogamicin, 41BB costimulation, CD3ζ signaling domain, and lentiviral (LV) vector. In vitro, CART33 resulted robust functions when incubated...
Supplementary Data from Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [<sup>18</sup>F]AlF-FAPI-74
Supplementary Figure from Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [<sup>18</sup>F]AlF-FAPI-74
Supplementary Data from Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [<sup>18</sup>F]AlF-FAPI-74
Supplementary Data from Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [<sup>18</sup>F]AlF-FAPI-74
<div>AbstractPurpose:<p>Despite the success of chimeric antigen receptor (CAR) T-cell therapy against hematologic malignancies, successful targeting solid tumors with CAR T cells has been limited by a lack durable responses and reports toxicities. Our understanding therapeutic efficacy in could be improved quantitative tools that allow characterization T–targeted antigens accurate monitoring response.</p>Experimental Design:<p>We used radiolabeled FAP inhibitor (FAPI)...
Supplementary Data from Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [<sup>18</sup>F]AlF-FAPI-74