A5101681100- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Renal Transplantation Outcomes and Treatments
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- Histone Deacetylase Inhibitors Research
- Cytomegalovirus and herpesvirus research
- Polyomavirus and related diseases
- Acute Myeloid Leukemia Research
- Biomedical Ethics and Regulation
- Cardiac Ischemia and Reperfusion
- PARP inhibition in cancer therapy
- Animal Virus Infections Studies
- Inflammasome and immune disorders
- Invertebrate Immune Response Mechanisms
- Multiple Myeloma Research and Treatments
- Calcium signaling and nucleotide metabolism
- Cancer Genomics and Diagnostics
- Renal Diseases and Glomerulopathies
- Mesenchymal stem cell research
- Chronic Myeloid Leukemia Treatments
AbbVie (United States)
2022-2023
Northwestern University
2008-2018
Northwestern Memorial Hospital
2015
University of Chicago
2014
Jesse Brown VA Medical Center
2009
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
2009
Abstract There is considerable interest in therapeutic transfer of regulatory T cells (Tregs) for controlling aberrant immune responses. Initial clinical trials have shown the safety Tregs hematopoietic stem cell transplant recipients and subjects with juvenile diabetes. Our hypothesis that infusion(s) may induce tolerance thus avoiding long-term use toxic immunosuppressive agents cause increased morbidity/mortality. Towards testing our hypothesis, we conducted a phase I dose escalation...
In Brief Nineteen subjects have more than 18 months’ follow-up in a phase IIb tolerance protocol HLA–mismatched recipients of living donor kidney plus facilitating cell enriched hematopoietic stem allografts (FCRx). Reduced intensity conditioning preceded allograft, followed the next day by FCRx. Twelve achieved stable chimerism and been successfully taken off immunosuppression (IS). We prospectively evaluated immune reconstitution immunocompetence. Return CD4+ CD8+ T central effector memory...
We previously described early results of a nonchimeric operational tolerance protocol in human leukocyte antigen (HLA)-identical living donor renal transplants and now update these results. Recipients given alemtuzumab, tacrolimus/MPA with sirolimus conversion were multiply infused hematopoietic CD34(+) stem cells. Immunosuppression was withdrawn by 24 months. Twelve months later, confirmed rejection-free transplant biopsies. Five the first eight enrollees initially tolerant 1 year off...
The precise STAT-regulated gene targets that inhibit cell growth and generate the antitumor effects of Type I interferons (IFNs) remain unknown. We provide evidence IFNs regulate expression Schlafens (SLFNs), a group genes involved in control cycle progression inhibitory responses. Using cells with targeted disruption different STAT proteins and/or p38 MAP kinase, we demonstrate IFN-dependent distinct Schlafen is differentially regulated by complexes kinase pathway. also for key functional...
Abstract Donor-specific CD4 + CD127 − CD25 FOXP3 regulatory T cells (AgTregs) have the potential to induce clinical transplant tolerance; however, their expansion ex vivo remains challenging. We optimized a novel protocol stimulate donor-specific Tregs using soluble 4-trimer CD40 ligand (CD40L)-activated donor B that expressed mature antigen-presenting cell markers. This avoided use of CD40L-expressing stimulator might otherwise result in cellular contamination. Purified allogeneic...
The interferon consensus sequence binding protein (ICSBP) is an regulatory transcription factor, also referred to as IRF8. ICSBP acts a suppressor of myeloid leukemia, although few target genes explaining this effect have been identified. In the current studies, we identified gene encoding growth arrest specific 2 (GAS2) relevant leukemia suppression. We find that ICSBP, Tel, and histone deacetylase 3 (HDAC3) bind cis element in GAS2 promoter repress progenitor cells. Gas2 inhibits calpain...
The cellular immune response is the most important mediator of allograft rejection and a major barrier to transplant tolerance. Delineation depth breadth alloreactive T cell repertoire subsequent application technology clinic may improve patient outcomes. As first step toward this, we have used MLR high-throughput sequencing characterize in healthy adults at baseline 3 months later. Our results demonstrate that thousands clones proliferate MLR, dominated by relatively high-abundance clones....
CD3 bispecific T-cell engagers (TCE), comprised of a tumor-targeting domain linked to binding domain, function by bridging target-positive tumors and CD3-expressing effector T cells enabling redirected cell-mediated killing tumor cells. Although the majority molecules in clinical development incorporate antibody-based domains, many tumor-associated antigens derive from intracellular proteins are not accessible targeting via antibody. Intracellular processed into short peptide fragments...
Summary The transcription factor HOXA 10 is an important regulator of myelopoiesis. Engineered over‐expression Hoxa10 in mice results a myeloproliferative disorder that progresses to acute myeloid leukaemia ( AML ) over time, and humans associated with poor outcomes . Here, we report loss expression reduced platelet count production, but does not affect clotting efficiency. About 40% fewer platelets were found null animals comparison wild type littermates. We nearly 50% reduction the...
<div>Abstract<p>CD3 bispecific T cell engagers (TCE), comprised of a tumor targeting domain linked to CD3 binding domain, function by bridging target-positive tumors and CD3-expressing effector cells enabling redirected cell-mediated killing cells. Although the majority molecules in clinical development incorporate tumor-targeting antibody-based domains, many tumor-associated antigens derive from intracellular proteins are not accessible via antibody. Intracellular processed into...
<p>A prostate tumor cell line (PC3M-A2/beta 2M) was inoculated subcutaneously in the right flank of CD34-humanized NSG mice. Mice were treated intravenously at indicated time points with either vehicle or an ABBV-184 precursor molecule, and size monitored. Tumors experienced transient regression growth inhibition prior to harvest for analysis tumor-infiltrating immune cells.</p>
<p>A prostate tumor cell line (PC3M-A2/beta 2M) was inoculated subcutaneously in the right flank of CD34-humanized NSG mice. Mice were treated intravenously at indicated time points with either vehicle or an ABBV-184 precursor molecule, and size monitored. Tumors experienced transient regression growth inhibition prior to harvest for analysis tumor-infiltrating immune cells.</p>
We have initiated a tolerance trial in HLA-mismatched kidney transplant (Tx) patients by infusing Facilitating Cell (FC)-containing hematopoietic stem cells (HSC) together with low intensity conditioning that included fludarabine, 200-centigray total body irradiation and cyclophosphamide. Recipients were maintained on post-Tx immunosuppression (IS) tacrolimus mycophenolate mofetil. 12 developed stable chimerism minimal toxicity without GVHD, their IS totally withdrawn at 1 year post-Tx. In...
<div>Abstract<p>CD3 bispecific T cell engagers (TCE), comprised of a tumor targeting domain linked to CD3 binding domain, function by bridging target-positive tumors and CD3-expressing effector cells enabling redirected cell-mediated killing cells. Although the majority molecules in clinical development incorporate tumor-targeting antibody-based domains, many tumor-associated antigens derive from intracellular proteins are not accessible via antibody. Intracellular processed into...
<p>A prostate tumor cell line (PC3M-A2/beta 2M) was inoculated subcutaneously in the right flank of CD34-humanized NSG mice. Mice were treated intravenously at indicated time points with either vehicle or an ABBV-184 precursor molecule, and size monitored. Tumors experienced transient regression growth inhibition prior to harvest for analysis tumor-infiltrating immune cells.</p>
<p>A prostate tumor cell line (PC3M-A2/beta 2M) was inoculated subcutaneously in the right flank of CD34-humanized NSG mice. Mice were treated intravenously at indicated time points with either vehicle or an ABBV-184 precursor molecule, and size monitored. Tumors experienced transient regression growth inhibition prior to harvest for analysis tumor-infiltrating immune cells.</p>
<div>Abstract<p>CD3 bispecific T-cell engagers (TCE), comprised of a tumor-targeting domain linked to CD3 binding domain, function by bridging target-positive tumors and CD3-expressing effector T cells enabling redirected cell–mediated killing tumor cells. Although the majority molecules in clinical development incorporate antibody-based domains, many tumor-associated antigens derive from intracellular proteins are not accessible targeting via antibody. Intracellular processed...