A5091764075- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Viral Infectious Diseases and Gene Expression in Insects
- Immunotherapy and Immune Responses
- Cancer-related Molecular Pathways
- Biosimilars and Bioanalytical Methods
- Metabolism, Diabetes, and Cancer
- PI3K/AKT/mTOR signaling in cancer
- Biotin and Related Studies
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- bioluminescence and chemiluminescence research
- Advanced Fluorescence Microscopy Techniques
- Cancer, Lipids, and Metabolism
- CRISPR and Genetic Engineering
Fred Hutch Cancer Center
2020-2024
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2023
Cancer Research Center
2023
UCLA Health
2020
University of California, Los Angeles
2019
Logic at the cell surface A major challenge in medical interventions is to target only diseased cells. Although there are biomarkers characteristic of certain cancers, for example, it unlikely that a single marker can specify particular type. Lajoie et al. addressed this problem by designing protein switches called Co-LOCKR bind antigens on and activate through conformational change when precise combination antigens. They designed perform AND, OR, NOT logic. On path toward applying...
Receptor pathway analysis informs structural modifications to CAR T cells that improve their function.
The interaction of the tumor necrosis factor receptor (TNFR) family member CD27 on naive CD8+ T (Tn) cells with homotrimeric CD70 antigen-presenting (APCs) is necessary for cell memory fate determination. Here, we examined signaling during Tn activation and differentiation. In conjunction (TCR) stimulation, ligation by a synthetic trimeric ligand triggered internalization degradation, suggesting active regulation this axis. Internalized recruited adaptor TRAF2 phosphatase SHP-1, thereby...
Abstract Purpose: The receptor tyrosine kinase–like orphan 1 (ROR1) is expressed in hematopoietic and epithelial cancers but has limited expression on normal adult tissues. This phase I study evaluated the safety of targeting ROR1 with autologous T lymphocytes engineered to express a chimeric antigen (CAR). Secondary objectives persistence, trafficking, antitumor activity CAR-T cells. Patients Methods: Twenty-one patients ROR1+ tumors received cells at one four dose levels: 3.3 × 105, 106,...
<p>Supplementary Figure 1: Strobe Flow Diagram.</p>
<p>Supplementary Figure 4: Flow cytometric analysis of T cell phenotypes in apheresis, infusion products and EGFRt + CAR cells at peak expansion.</p>
<div>AbstractPurpose:<p>The receptor tyrosine kinase–like orphan 1 (ROR1) is expressed in hematopoietic and epithelial cancers but has limited expression on normal adult tissues. This phase I study evaluated the safety of targeting ROR1 with autologous T lymphocytes engineered to express a chimeric antigen (CAR). Secondary objectives persistence, trafficking, antitumor activity CAR-T cells.</p>Patients Methods:<p>Twenty-one patients ROR1<sup>+</sup> tumors...
<p>Supplementary Figure 3: Lymphodepletion and CAR T cell expansion.</p>
<p>Supplementary Data 1: Study Protocol.</p>
<p>Supplementary Figure 2: Toxicity Assessment.</p>
Engagement of CD27 during naïve CD8+ T (TN) cell activation is critical for memory generation through mechanisms that are incompletely understood. To examine the effects signaling TN we designed a synthetic trimeric CD70 ligand. ligation resulted in immediate receptor internalization and recruitment TRAF2/SHP-1. Activated SHP-1 dephosphorylated Lck modulated ERK/AKT cells receiving concurrent CD28 costimulation. Subsequently, enhanced ATF2, FOXO1, FOXP1 transcription factor circuits, which...
Abstract Triple negative breast cancer (TNBC) occurs in 10-15% of all (BC) patients, yet it accounts for almost half BC deaths. Women African ancestry (WAA) are twice as likely women European Ancestry (WEA) to be diagnosed with advanced TNBC worse prognosis. Emerging data shows that insulin resistance and high circulating levels more prevalent WAA invasive BCs than WEA, activation the AKT/mTOR pathway by may occur aggressive TNBC. Reports show diabetic patients treated metformin, a biguanide...
Abstract Triple negative breast cancer (TNBC) occurs in about 15% of (BC) patients, yet it accounts for almost 50% all BC deaths. TNBC is characterized by lack expression estrogen, progesterone and HER2 receptors, cannot be treated with current targeted therapies. TNBCs are heterogeneous occur often younger African American women. Although initially responsive to some chemotherapies, tend relapse early metastasize, leading poor survival. Development new therapeutic approaches clinical...