- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Nanowire Synthesis and Applications
- T-cell and B-cell Immunology
- Renal Transplantation Outcomes and Treatments
- Silicon Carbide Semiconductor Technologies
- Advancements in Semiconductor Devices and Circuit Design
University of Pennsylvania
2017-2023
The success of chimeric antigen receptor (CAR)-mediated immunotherapy in acute lymphoblastic leukemia (ALL) highlights the potential T-cell therapies with directed cytotoxicity against specific tumor antigens. efficacy CAR therapy depends on engraftment and persistence T cells following adoptive transfer. Most protocols for engineering routinely expand
A notable number of acute lymphoblastic leukemia (ALL) patients develop CD19-positive relapse within 1 year after receiving chimeric antigen receptor (CAR) T cell therapy. It remains unclear if the long-term response is associated with characteristics CAR cells in infusion products, hindering identification biomarkers to predict therapeutic outcomes. Here, we present 101,326 single-cell transcriptomes and surface protein landscape from products 12 ALL patients. We observed substantial...
Background Autologous T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19 molecule have transformed the therapeutic landscape in patients with highly refractory leukemia and lymphoma, use of donor-generated allogeneic CAR is paving way further breakthroughs treatment cancer. However, it remains unknown how intrinsic heterogeneities these mediate efficacy whether products match effectiveness autologous therapies. Methods Using single-cell mRNA sequencing...
Chimeric antigen receptor (CAR) T cell therapy is used in treating human hematological malignancies, but its efficacy limited by exhaustion (T EX ). arises at the expense of central memory cells CM ), which exhibit robust antitumor efficacy. Reduction TET2 gene led to increased differentiation a patient with leukemia who experienced complete remission. We show that loss chromatin accessibility regulators TOX and TOX2, plus expression TOX2. Knockdown percentage . However, unexpectedly,...
CD19-redirected chimeric antigen receptor (CAR) T cells have shown remarkable activity against B-cell cancers. While second-generation CARs induce complete remission in >80% of patients with acute lymphoblastic leukemia, similar monotherapy induces long-term remissions only 26% chronic lymphocytic leukemia (CLL). This disparity is attributed to cell-intrinsic effector defects autologous CLL-derived cells. However, the mechanisms by which leukemic impact CAR T-cell potency are poorly...
Abstract Chimeric antigen receptor-modified (CAR) T cells targeting CD19 have mediated dramatic responses in relapsed/refractory acute lymphoblastic leukemia (ALL), yet a notable number of patients CD19-positive relapse within one year treatment. It remains unclear if the long-term response is associated with characteristics CAR infusion products, hindering identification biomarkers to predict therapeutic outcomes prior Herein we present 101,326 single cell transcriptomes and surface protein...
<div><p>CD19-redirected chimeric antigen receptor (CAR) T cells have shown remarkable activity against B-cell cancers. While second-generation CARs induce complete remission in >80% of patients with acute lymphoblastic leukemia, similar monotherapy induces long-term remissions only 26% chronic lymphocytic leukemia (CLL). This disparity is attributed to cell-intrinsic effector defects autologous CLL-derived cells. However, the mechanisms by which leukemic impact CAR T-cell...
<div>Abstract<p>The success of chimeric antigen receptor (CAR)–mediated immunotherapy in acute lymphoblastic leukemia (ALL) highlights the potential T-cell therapies with directed cytotoxicity against specific tumor antigens. The efficacy CAR therapy depends on engraftment and persistence T cells following adoptive transfer. Most protocols for engineering routinely expand <i>ex vivo</i> 9 to 14 days. Because is related state differentiation, we hypothesized that...
<div><p>CD19-redirected chimeric antigen receptor (CAR) T cells have shown remarkable activity against B-cell cancers. While second-generation CARs induce complete remission in >80% of patients with acute lymphoblastic leukemia, similar monotherapy induces long-term remissions only 26% chronic lymphocytic leukemia (CLL). This disparity is attributed to cell-intrinsic effector defects autologous CLL-derived cells. However, the mechanisms by which leukemic impact CAR T-cell...
<div>Abstract<p>The success of chimeric antigen receptor (CAR)–mediated immunotherapy in acute lymphoblastic leukemia (ALL) highlights the potential T-cell therapies with directed cytotoxicity against specific tumor antigens. The efficacy CAR therapy depends on engraftment and persistence T cells following adoptive transfer. Most protocols for engineering routinely expand <i>ex vivo</i> 9 to 14 days. Because is related state differentiation, we hypothesized that...
<p>Table S1 and Figures -S8</p>
<p>Table S1 and Figures -S8</p>
<p>Supplemental Figure 1: An overview of study design choices. Supplemental 2: IL-2 Supplementation Enhances the APC phenotype CLL cells. 3: Exogenous Co-stimulation Improves Second-generation CAR T cell Activation. 4: aCLL Stimulation Shows Inconsistent Cytokine Production After a 6hr Incubation. Table Full Antibody List. Donor list adjusted P-values from Holm-Sidak multiple comparisons.</p>
<p>Supplemental Figure 1: An overview of study design choices. Supplemental 2: IL-2 Supplementation Enhances the APC phenotype CLL cells. 3: Exogenous Co-stimulation Improves Second-generation CAR T cell Activation. 4: aCLL Stimulation Shows Inconsistent Cytokine Production After a 6hr Incubation. Table Full Antibody List. Donor list adjusted P-values from Holm-Sidak multiple comparisons.</p>