A5056393729- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Clinical Nutrition and Gastroenterology
- vaccines and immunoinformatics approaches
- Cancer Research and Treatments
- Gut microbiota and health
- Virus-based gene therapy research
- Immune cells in cancer
- Immune Response and Inflammation
- Diet and metabolism studies
- Dermatologic Treatments and Research
- Heat shock proteins research
- Melanoma and MAPK Pathways
- Neuroblastoma Research and Treatments
- Kruppel-like factors research
- Infant Nutrition and Health
- Monoclonal and Polyclonal Antibodies Research
- Rabbits: Nutrition, Reproduction, Health
- Cellular Mechanics and Interactions
- melanin and skin pigmentation
- Hematopoietic Stem Cell Transplantation
- Enhanced Recovery After Surgery
University of Maryland, Baltimore
2010-2018
University of Maryland Medical Center
2013-2018
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
2010-2016
Center of Molecular Immunology (Cuba)
2010-2015
University of Baltimore
2013-2015
National Cancer Institute
2002-2010
National Institutes of Health
2002-2010
Center for Cancer Research
2004-2010
Bipar
2010
Johns Hopkins University
2007
Depletion of immune elements before adoptive cell transfer (ACT) can dramatically improve the antitumor efficacy transferred CD8+ T cells, but specific mechanisms that contribute to this enhanced immunity remain poorly defined. Elimination CD4+CD25+ regulatory (T reg) cells has been proposed as a key mechanism by which lymphodepletion augments ACT-based immunotherapy. We found even in genetic absence reg nonmyeloablative regimen substantially augmented reactivity self-tissue and tumor....
Many tumor-associated antigens are derived from nonmutated “self” proteins. T cells infiltrating tumor deposits recognize self-antigens presented by and can be expanded in vivo with vaccination. These exist a functionally tolerant state, as they rarely result eradication. We found that growth lethality were unchanged mice even after adoptive transfer of large numbers specific for an MHC class I–restricted epitope the self/tumor antigen gp100. sought to develop new strategies would reverse...
Central memory CD8 + T cells (T CM ) and effector EM are found in humans mice; however, their relative contributions to host immunity have only recently been examined vivo . Further, the ability of treat an established tumor or infection has yet be evaluated. To address therapeutic potential different tumor-reactive cell subsets, we used model for vitro generation by using IL-15 IL-2, respectively. Adoptively transferred exhibited a potent recall response when combined with tumor-antigen...
Adoptive transfer of large numbers tumor-reactive CD8+ cytotoxic T lymphocytes (CTLs) expanded and differentiated in vitro has shown promising clinical activity against cancer. However, such protocols are complicated by extensive ex vivo manipulations cells have largely focused on CTLs, with much less emphasis the role contribution CD4+ cells. Using a mouse model advanced melanoma, we found that small naive into lymphopenic recipients induces substantial cell expansion, differentiation,...
Abstract CD4+ T cells control the effector function, memory, and maintenance of CD8+ cells. Paradoxically, we found that absence enhanced adoptive immunotherapy cancer when using directed against a persisting tumor/self-Ag. However, transfer CD4+CD25− Th (Th cells) with tumor/self-reactive vaccination into cell-deficient hosts induced autoimmunity regression established melanoma. Transfer contained mixture CD4+CD25+ regulatory (Treg or Treg alone prevented effective immunotherapy....
IL-15 and IL-2 possess similar properties, including the ability to induce T cell proliferation. However, whereas can promote apoptosis limit CD8(+) memory survival proliferation, helps maintain a population inhibit apoptosis. We sought determine whether could enhance in vivo function of tumor/self-reactive cells by using receptor transgenic mouse (pmel-1) whose recognize an epitope derived from self/melanoma antigen gp100. By removing endogenous tumor-bearing knockout hosts or supplementing...
Lymphodepletion with total body irradiation (TBI) increases the efficacy of adoptively transferred tumor-specific CD8(+) T cells by depleting inhibitory lymphocytes and increasing homeostatic cytokine levels. We found that TBI augmented function in mice genetically deficient all lymphocytes, indicating existence another mechanism action. Additional investigation revealed commensal gut microflora mesenteric lymph nodes elevated LPS levels sera irradiated mice. These findings correlated...
In vitro differentiated CD8(+) T cells have been the primary focus of immunotherapy cancer with little on CD4(+) cells. Immunotherapy involving in given after lymphodepleting regimens significantly augments antitumor immunity animals and human patients cancer. However, mechanisms by which lymphopenia adoptive cell therapy means properly differentiating are still emerging. We demonstrate that naive tumor/self-specific naturally into helper type 1 cytotoxic vivo caused regression established...
Recurrent solid malignancies are often refractory to standard therapies. Although adoptive T cell transfer may benefit select individuals, the majority of patients succumb their disease. To address this important clinical dilemma, we developed a mouse melanoma model in which initial regression advanced disease was followed by tumor recurrence. During recurrence, Foxp3(+) tumor-specific CD4(+) cells became PD-1(+) and represented >60% host. Concomitantly, effector showed traits chronic...
Immunotherapies that augment antitumor T cells have had recent success for treating patients with cancer. Here we examined whether tumor-specific CD4(+) enhance CD8(+) T-cell adoptive immunotherapy in a lymphopenic environment. Our model employed physiological doses of tyrosinase-related protein 1-specific transgenic cells-CD4(+) and pmel-CD8(+) when transferred individually were subtherapeutic; however, together provided significant (p ≤ 0.001) therapeutic efficacy. Therapeutic efficacy...
Abstract Keratinocyte growth factor (KGF) promotes intestinal epithelial growth. To understand the relevance of intraepithelial lymphocyte (IEL)-derived KGF expression on growth, we used a mouse model villus atrophy by administration total parenteral nutrition, and hypertrophy creation short bowel syndrome. was confined to γδ-ΤCR+ IELs. IEL-derived highest in crypts, somewhat less lower portion villi, markedly upper villi. Total nutrition associated with down-regulation expression, syndrome...
Abstract IL-2 is a critical T cell growth factor in vitro, but predominantly mediates tolerance vivo. mainly produced by CD4+ Th cells, the role of cell-derived vivo controversial. We demonstrate that during immunity to tumor/self-Ag, predominant was maintain IL-2Rα (CD25) on regulatory cells (Treg), which resulted their maintenance Treg lineage factor, Forkhead/winged helix transcription (Foxp3), and tolerance. However, absence maintained effector caused autoimmunity. IL-2R signaling...
Objective To determine the etiology of loss epithelial barrier function observed with administration total parenteral nutrition (TPN) in a mouse model. Summary Background Data Removal enteral TPN is associated intestinal function. The this not clear. Because intraepithelial lymphocytes (IELs) produce number cytokines that may alter permeability, authors investigated IEL cytokine expression model TPN. Methods Adult C57BL/6 mice received or diet for 7 days. IELs were subsequently harvested and...
Melanocyte differentiation Ags, including tyrosinase-related protein (TRP) 1, are relevant to both autoimmune skin depigmentation (vitiligo) and tumor immunity, because they expressed by benign melanocytes many malignant melanomas. Melanoma patients generate CD4(+) T cells that specifically recognize these proteins. TRP1 contains internal disulfide bonds is presented MHC class II molecules. Gamma-IFN-inducible lysosomal thiol reductase (GILT) facilitates the generation of II-binding peptides...
Therapeutic treatment of large established tumors using immunotherapy has yielded few promising results. We investigated whether adoptive transfer tumor-specific CD8(+) T cells, together with CD4(+) would mediate regression B16BL6-D5 melanomas in lymphopenic Rag1(-/-) recipients devoid regulatory cells. The combined subtherapeutic doses both TRP1-specific TCR transgenic cells and gp100-specific into recipients, who received vaccination, led to (100-400 mm(2)) melanomas. same strategy was...
Immunotherapy using adoptive cell transfer is a promising approach that can result in the regression of bulky, invasive cancer some patients. However, currently available therapies remain less successful than desired. To study mechanisms action and possible improvements cell-transfer therapies, we use murine model system with analogous components to treatment T receptor transgenic CD8+ cells (pmel-1) specifically recognizing melanocyte differentiation antigen gp100 are adoptively transferred...
Although FOXP3 is primarily expressed by regulatory CD4 T cells (Treg) in vivo, polyclonal activation of human CD8 can result the expression a fraction cells. However, cellular lineage and mechanism induction remain unclear. Here, we demonstrate that interleukin-2 (IL-2) induces OKT3-stimulated or antigen-stimulated cells, indicating neither limited to unique subset nor dependent on mode T-cell receptor stimulation. In absence IL-2, antigen stimulation resulted acquisition effector function...