A5064581434- Multiple Myeloma Research and Treatments
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Protein Degradation and Inhibitors
- RNA Interference and Gene Delivery
- Salivary Gland Disorders and Functions
- Immune Cell Function and Interaction
- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Diabetes and associated disorders
- Cancer Treatment and Pharmacology
- vaccines and immunoinformatics approaches
- Acute Myeloid Leukemia Research
- Chronic Lymphocytic Leukemia Research
- T-cell and B-cell Immunology
- Ubiquitin and proteasome pathways
- Viral Infectious Diseases and Gene Expression in Insects
- Chronic Myeloid Leukemia Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Growth Hormone and Insulin-like Growth Factors
- Immune Response and Inflammation
- Cancer Immunotherapy and Biomarkers
- Ocular Surface and Contact Lens
Moffitt Cancer Center
2016-2025
University of Tampa
2017-2019
University of South Florida
2003-2017
Johns Hopkins University
2005
Sidney Kimmel Cancer Center
2005
Sidney Kimmel Comprehensive Cancer Center
2005
The University of Texas Health Science Center at San Antonio
2001
University of Florida
1997-2001
Columbia University
2001
Florida College
2001
Abstract T cells infiltrating tumors have a decreased expression of signal transduction proteins, diminished ability to proliferate, and production cytokines. The mechanisms causing these changes remained unclear. We demonstrated recently that peritoneal macrophages stimulated with interleukin 4 + 13 produce arginase I, which decreases the T-cell receptor CD3ζ chain impairs responses. Using 3LL murine lung carcinoma model we tested whether I was produced in tumor microenvironment could...
The NOD (nonobese diabetic) mouse has been studied as an animal model for autoimmune insulin-dependent diabetes and Sjögren’s syndrome. NOD.Igμ null mice, which lack functional B lymphocytes, develop progressive histopathologic lesions of the submandibular lachrymal glands similar to but in absence insulitis diabetes. Despite focal appearance T cells salivary tissues, mice fail lose secretory function determined by stimulation muscarinic/cholinergic receptor agonist pilocarpine, suggesting a...
The divalent cation-dependent interaction of the beta 2 integrin CR3 (CD11b/CD18) with major complement opsonic C3 fragment iC3b is an important component central role in inflammation and immune clearance. In this investigation we have identified binding site CR3. A recombinant representing A-domain, a 200-amino acid region ectodomain CD11b subunit, bound to directly manner. was further localized short linear peptide that also inhibited A-domain as well expressed by human neutrophils. These...
Idecabtagene vicleucel (ide-cel) was FDA-approved in March 2021 for the treatment of relapsed/refractory multiple myeloma after 4 lines therapy. On KarMMa trial, grade ≥ 3 cytopenias and infections were common. We sought to characterize within 100 days ide-cel standard-of-care (SOC) setting. This multi-center retrospective study included 52 patients who received SOC ide-cel; 47 reached day-90 follow-up. Data censored at day 100. Grade cytopenia present among 65% 30 40% 90. Granulocyte colony...
Abstract Sjögren's syndrome‐like autoimmune exocrinopathy (AEC) in the nonobese diabetic (NOD) mouse progresses from a preimmune phase to an immune phase, resulting dry mouth and/or eyes. In present study, impact of prototypical T‐helper type 1 cytokine, interferon‐gamma (IFN‐γ), on onset AEC was investigated using both IFN‐γ and receptor gene knockout mice, NOD. –/– IFN‐γR , respectively. Neither nor mice exhibited increased acinar cell apoptosis abnormal salivary protein expression,...
The appearance of autoimmune diabetes prior to exocrinopathy in the NOD mouse suggests that it is an excellent model secondary, but not primary, sicca complications. Since unique major histocompatibility complex (MHC) I-A(g7) expression mice essential for development insulitis and these animals, we investigated exocrine gland function NOD.B10.H2b mice, which have MHC congenic NOD, as a potential primary Sjögren's syndrome (SS).Histopathologic manifestations lymphocytic infiltrates into...
Objective Antibodies directed against general and specific target-organ autoantigens are present in the sera of human patients animal models with autoimmune disease. The relevance these autoantibodies to disease process remains ambiguous most cases. In exocrinopathy (Sjögren's syndrome), intracellular nuclear proteins SSA/Ro SSB/La, as well cell surface muscarinic cholinergic receptor (M3) observed. To evaluate potential role factors loss secretory function exocrine tissues, a panel...
Abstract Previously we demonstrated that SHIP−/− mice accept allogeneic bone marrow transplants (BMT) without significant acute graft-vs-host disease (GvHD). In this study show splenocytes and lymph node cells are poor stimulators of T cell responses cause GvHD. Intriguingly, prime naive to peptide epitopes, but, conversely, partially impaired for priming whole Ag. However, dendritic (DC) purified from targets, Ag as effectively SHIP+/+ DC. These findings point an extrinsic effect on DC...
Peptide vaccines are capable of eliciting immune responses targeting tumor-associated antigens such as the Wilms' Tumor 1 (WT1) antigen, often overexpressed in myeloid malignancies. Here, we assessed safety, tolerability, and immunogenicity a polyvalent WT1 peptide vaccine. Individuals with WT1-positive acute leukemia (AML) first (CR1) or second (CR2) remission higher-risk myelodysplastic syndrome (MDS) following at least prior line therapy were vaccinated mixture peptides derived from...
Abstract Idecabtagene vicleucel (ide-cel) is a type of B-cell maturation antigen (BCMA)–targeting chimeric receptor T-cell (CAR-T) approved for the treatment relapsed and refractory multiple myeloma (RRMM). Currently, incidence cardiac events associated with ide-cel remains unclear. This was retrospective single-center observational study patients treated RRMM. We included all consecutive who received standard-of-care at least 1-month follow-up. Baseline clinical risk factors, safety...
NOD mice manifest many features of autoimmune exocrinopathy (Sjögren's syndrome), a disease generally characterized by chronic, progressive immunological attack against the exocrine tissues salivary and lacrimal glands. Previous studies using congenic partner strain, NOD.Igμ null , defined an important role for B lymphocytes in development xerostomia, implicating autoantibodies reactive with acetylcholine muscarinic receptor (M 3 R) as possible effector mechanism. In present study, we have...
NKR-2 are autologous T cells genetically modified to express a chimeric antigen receptor (CAR) comprising fusion of the natural killer group 2D (NKG2D) with CD3ζ signalling domain, which associates adaptor molecule DNAX-activating protein 10 kDa (DAP10) provide co-stimulatory signal upon ligand binding. NKG2D binds eight different ligands expressed on cell surface many tumour and normally absent non-neoplastic cells. In preclinical studies, demonstrated long-term antitumour activity towards...
Abstract Multiple myeloma (MM) incidence, mortality, and survival vary by race ethnicity, but the causes of differences remain unclear. We investigated demographic, clinical, molecular features diverse MM patients to elucidate mechanisms driving clinical disparities. This study included 495 (self-reported Hispanic, n = 45; non-Hispanic Black, 52; White, 398). Hispanic Black individuals had an earlier age onset than White (53 57 vs 63 years, respectively, P < .001). There were no in...
Abstract Purpose: We investigated whether a dendritic cell (DC) vaccine transduced with an adenoviral vector encoded full-length survivin (Ad-S), mutations neutralizing its antiapoptotic function, could safely generate immune response and deepen clinical responses when administered before after autologous stem transplant (ASCT) for multiple myeloma. Patients Methods: This phase I first-in-human trial (NCT02851056) evaluated the safety of DC:Ad-S in newly diagnosed myeloma not having achieved...