A5062706815- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Renal Transplantation Outcomes and Treatments
- Mesenchymal stem cell research
- Chronic Lymphocytic Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- Acute Myeloid Leukemia Research
- Virus-based gene therapy research
- Cancer Immunotherapy and Biomarkers
- Immunodeficiency and Autoimmune Disorders
- Salivary Gland Disorders and Functions
- Neutropenia and Cancer Infections
- Acute Lymphoblastic Leukemia research
- Oral health in cancer treatment
- Multiple Myeloma Research and Treatments
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Reproductive System and Pregnancy
- Polyomavirus and related diseases
- Transplantation: Methods and Outcomes
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Research and Treatments
National Cancer Institute
2016-2025
National Institutes of Health
2015-2024
Center for Cancer Research
2011-2023
National Cancer Institute
2005-2022
Cancer Institute (WIA)
2021
Janssen (Belgium)
2000-2018
Aduro BioTech (United States)
2018
Juno Therapeutics (Germany)
2018
Gilead Sciences (United Kingdom)
2018
Sidney Kimmel Comprehensive Cancer Center
2018
Purpose Therapies with novel mechanisms of action are needed for multiple myeloma (MM). T cells can be genetically modified to express chimeric antigen receptors (CARs), which artificial proteins that target antigens. B-cell maturation (BCMA) is expressed by normal and malignant plasma but not essential cells. We conducted the first-in-humans clinical trial, our knowledge, expressing a CAR targeting BCMA (CAR-BCMA). Patients Methods Sixteen patients received 9 × 10 6 CAR-BCMA cells/kg at...
Abstract Purpose: Multiple myeloma is a usually incurable malignancy of plasma cells. New therapies are urgently needed for multiple myeloma. Adoptive transfer chimeric antigen receptor (CAR)–expressing T cells promising new therapy hematologic malignancies, but an ideal target CAR-expressing T-cell has not been identified. B-cell maturation (BCMA) protein that reported to be selectively expressed by B-lineage including Our goal was determine if BCMA suitable Experimental Design: We...
Progressive malignancy is the leading cause of death after allogeneic hematopoietic stem-cell transplantation (alloHSCT). After alloHSCT, B-cell malignancies often are treated with unmanipulated donor lymphocyte infusions (DLIs) from transplant donor. DLIs frequently not effective at eradicating and graft-versus-host disease, a potentially lethal immune response against normal recipient tissues.
Clinical trials have indicated that autologous hematopoietic stem cell transplantation (HSCT) can persistently suppress inflammatory disease activity in a subset of patients with severe multiple sclerosis (MS), but the mechanism has remained unclear. To understand whether beneficial effects on course are mediated by lympho-depletive alone or sustained regeneration immune repertoire, we examined long-term reconstitution MS who received HSCT. After numeric recovery leukocytes, at 2-yr...
Interleukin-7 (IL-7) is a homeostatic cytokine for resting T cells with increasing serum and tissue levels during cell depletion. In preclinical studies, IL-7 therapy exerts marked stimulating effects on immune reconstitution in mice primates. First-in-human clinical studies of recombinant human (rhIL-7) provided the opportunity to investigate lymphocytes vivo. rhIL-7 induced vivo cycling, bcl-2 up-regulation, sustained increase peripheral blood CD4+ CD8+ cells. This expansion caused...
Homeostatic regulation of T cells involves an ongoing balance new cell generation, peripheral expansion, and turnover. The recovery when this is disrupted provides insight into the mechanisms that govern homeostasis. In a long-term, single cohort study, we assessed role thymic function after autologous transplant in adults, correlating serial computed tomography imaging size with concurrent measurements CD4+ populations. We established age-dependent incidence, time course, duration...
To determine the maximum-tolerated dose, toxicities, and pharmacokinetic profile of farnesyl protein transferase inhibitor R115777 when administered orally bid for 5 days every 2 weeks.Twenty-seven patients with a median age 58 years received 85 cycles using an intrapatient interpatient dose escalation schema. Drug was at escalating doses as solution (25 to 850 mg bid) or pellet capsules (500 1300 bid). Pharmacokinetics were assessed after first last during cycle 1.Dose-limiting toxicity...
Interleukin-7 (IL-7) has critical and nonredundant roles in T-cell development, hematopoiesis, postdevelopmental immune functions as a prototypic homeostatic cytokine. Based on large body of preclinical evidence, it may have multiple therapeutic applications immunodeficiency states, either physiologic (immunosenescence), pathologic (HIV), or iatrogenic (postchemotherapy posthematopoietic stem cell transplant), reconstitution enhancement immunotherapy. We report here the toxicity biological...
Transgenic mice containing intact copies of the human immunodeficiency virus (HIV) proviral DNA were constructed. Founder animals not viremic for HIV and remained healthy during a 9-month observation period. After being mated with nontransgenic animals, one founder mouse (No. 13) gave rise to F1 progeny that developed disease syndrome characterized by marked epidermal hyperplasia, lymphadenopathy, splenomegaly, pulmonary lymphoid infiltrates, growth retardation, death day 25 life. Infectious...
Biology-based markers to confirm or aid in the diagnosis prognosis of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation monitor its progression are critically needed facilitate evaluation new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated an indicator a normal biological pathogenic process, pharmacologic response therapeutic intervention. Applications biomarkers GVHD clinical trials patient...
Abstract The use of bone marrow-derived mesenchymal stromal cells (BMSC) in the treatment alloimmune and autoimmune conditions has generated much interest, yet an understanding therapeutic mechanism remains elusive. We therefore explored immune modulation by a clinical-grade BMSC product model human-into-mouse xenogeneic graft-versus-host disease (x-GVHD) mediated human CD4+ Th1 cells. reversed established, lethal x-GVHD through marked inhibition cell effector function. Gene marking studies...
Homeostatic regulation of T cells involves an ongoing balance new cell generation, peripheral expansion, and turnover. The recovery when this is disrupted provides insight into the mechanisms that govern homeostasis. In a long-term, single cohort study, we assessed role thymic function after autologous transplant in adults, correlating serial computed tomography imaging size with concurrent measurements CD4(+) populations. We established age-dependent incidence, time course, duration...
Although xerostomia is a commonly reported complaint in patients with chronic graft-versus-host disease (cGVHD), criteria for evaluating the prevalence and characteristics of salivary gland involvement have not been well defined this patient population. Previous studies also made no distinction between mucosal oral cGVHD. We systematically evaluated signs symptoms sicca large cohort cGVHD (n = 101) using instruments widely used to study Sjogren's syndrome. Xerostomia was by 77% associated...