A5024667876- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Cancer Research and Treatments
- RNA Interference and Gene Delivery
- Phagocytosis and Immune Regulation
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- Advanced biosensing and bioanalysis techniques
- Immune cells in cancer
- Reproductive System and Pregnancy
- Influenza Virus Research Studies
- Cancer-related molecular mechanisms research
- vaccines and immunoinformatics approaches
- Immune responses and vaccinations
- Ovarian cancer diagnosis and treatment
- Nanoplatforms for cancer theranostics
- Hematopoietic Stem Cell Transplantation
- Glycosylation and Glycoproteins Research
- Diabetes and associated disorders
- CRISPR and Genetic Engineering
- Immunodeficiency and Autoimmune Disorders
NexImmune (United States)
2016-2025
Johns Hopkins University
2010-2023
Johns Hopkins Medicine
2008-2018
University of Baltimore
2010-2017
Sidney Kimmel Comprehensive Cancer Center
2012
Aaron Diamond AIDS Research Center
2012
Rockefeller University
2012
The Ohio State University
2010
Institute of Molecular Biology and Pathology
2009
Medizinische Hochschule Hannover
2004-2009
Adoptive immunotherapy (AIT) can mediate durable regression of cancer, but widespread adoption AIT is limited by the cost and complexity generating tumor-specific T cells. Here we develop an Enrichment + Expansion strategy using paramagnetic, nanoscale artificial antigen presenting cells (aAPC) to rapidly expand from rare naïve precursors predicted neo-epitope responses. Nano-aAPC are capable enriching in a magnetic column subsequently activating them induce proliferation. resulted greater...
Abstract Tumors often display mechanisms to avoid or suppress immune recognition. One such mechanism is the shedding of gangliosides into local tumor microenvironment, and a high concentration circulating associated with poor prognosis. In this study, we identify ganglioside GD3, which was isolated from polar lipid fraction ovarian cancer–associated ascites, as an inhibitory factor that prevents innate activation natural killer T (NKT) cells. Purified GD3 displayed affinity for both human...
Background. Telomeres provide a key mechanism for protecting the integrity of chromosomes and their attrition after cell division during aging are evident in lymphocytes. However, significance telomere shortening age-associated decline immune function is unknown. Methods. We selected 22 HLA-A2–positive healthy older adults who have relatively short or long lengths to compare antibody response against influenza vaccine, CD8+ T-cell an antigen. Results. B cells from individuals with robust...
Abstract The development of effective antitumor immune responses is normally constrained by low-avidity, tumor-specific CTLs that are unable to eradicate the tumor. Strategies rescue activity low-avidity melanoma-specific in vivo may improve immunotherapy efficacy. To boost effectiveness CTLs, we immunized mice bearing lung melanoma metastases with artificial antigen-presenting cells (aAPC), made covalently coupling pepMHC-Ig dimers and B7.1-Ig molecules magnetic beads. aAPC treatment...
The ability of individual T cells to perform multiple effector functions is crucial for protective immunity against viruses and cancer. This polyfunctionality frequently lost during chronic infections; however, the molecular mechanisms driving cell are poorly understood. We found that human stimulated by a high concentration antigen lacked expressed transcription profile similar exhausted cells. One specific pathway implicated in control was MAPK/ERK pathway. altered response different...
Abstract Purpose: Generation of antigen-specific T cells from patients with cancer employs large numbers peripheral blood and/or tumor-infiltrating to generate antigen-presenting and effector commonly requiring multiple rounds restimulation ex vivo. We used a novel paramagnetic, nanoparticle-based artificial cell (nano-aAPC) that combines anti-CD28 costimulatory human MHC class I molecules are loaded antigenic peptides rapidly expand tumor antigen–specific melanoma. Experimental Design:...
Invasive cervical cancer (ICC) is the most common cause of death due to for women living in poverty worldwide. However, there are no approved targeted therapies or schemes divide treatment. To address this, we have performed exome and long-read whole genome sequencing (WGS) 450 ICC tumors from Guatemala. In addition, 50-100X WGS on 29 cell lines. This includes nearly all publicly available We extended these findings using 807 samples cBioPortal (TCGA, AACR-Genie, MSKCC met). The two commonly...
Melanoma and renal cell carcinoma (RCC) are considered to be the most immunogenic tumors in humans. To generate conditions induce primary T-cell responses against RCC allow further expansion of tumor-specific cytotoxic T lymphocytes (CTL) for adoptive transfer, peripheral blood mononuclear cells from patients were stimulated with autologous tumor or monocyte-derived dendritic (DC) loaded either lysate (TU-LY) apoptotic (TU-AP). Whereas repetitive stimulation (4×) alone induced a predominant...
Dietary fatty acids are major contributors to the development and progression of insulin resistance nonalcoholic liver disease (NAFLD). also alter hepatic NKT cells that activated by antigens presented CD1d. In current study, we examine mechanism dietary acid induced cell deficiency its causal relationship NAFLD. We discover saturated (SFA) or monounsaturated (MUFA), but not polyunsaturated (PUFA), cause depletion with increased apoptosis. SFA MUFA impair hepatocyte presentation endogenous,...
The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms known involved. T-cell responses play an important role modulating antibody production killing infected cells. However, little about repertoire elicited by YF-17DD vaccine in humans. In this report, a library 653 partially overlapping 15-mer peptides covering envelope (Env) nonstructural (NS)...
Cytomegalovirus (CMV) infection/reactivation remains among the most important complications of immunosuppression after transplantation. However, recent clinical observations indicate that mammalian target rapamycin (mTOR) inhibition with sirolimus may improve outcome CMV complications. Underlying mechanisms this observation, particularly effect on naïve- and CMV-specific cytotoxic CD8+ T-cell (CMV-CTL) functionality is still undiscovered. Here, influence naïve memory CMV-CTLs was determined...
Transplantation of hematopoietic stem cells (HSCs) from peripheral blood (PB) or cord (CB) is well established. HSCs CB are associated with a lower risk graft-versus-host disease (GVHD), but antigen-independent expanded CB- and PB-derived T can induce GVHD in allo-HSC recipients. CB-derived might be more suitable for adoptive immunotherapy as they have unique T-cell characteristics. Here, we describe functional differences between PB stimulated different cytokine combinations involved...
Abstract Purpose: Natural killer T (NKT) cells are important mediators of antitumor immune responses. We have previously shown that ovarian cancers shed the ganglioside GD3, which inhibits NKT-cell activation. Ovarian also secrete high levels VEGF. In this study, we sought to test hypothesis VEGF production by suppresses NKT-cell–mediated Experimental Design: To investigate effects on CD1d-mediated activation, a conditioned media model was established, wherein supernatants from cancer cell...
Redirection of T cells to target and destroy tumors has become an important clinical tool major area research in tumor immunology. Here we present a novel, nanoparticle-based approach selectively bind antigen-specific cytotoxic (CTL) redirect them kill tumors, termed ATR (Antigen-specific cell Redirectors). were generated by decorating nanoparticles with both binding moiety, either peptide loaded MHC-Ig dimer or clonotypic anti-TCR antibody, model anti-CD19 antibody engage CD19+ cells....
Besides mobilizing stem cells into the periphery, granulocyte colony-stimulating factor (G-CSF) has been shown to influence various types of innate and adaptive immune cells. For example, it impairs effector function cytotoxic T lymphocytes (CTLs). It is assumed that this effect mediated indirectly by monocytes, regulatory immunomodulatory cytokines influenced G-CSF. In study, isolated G-CSF-treated CD8(+) were stimulated antigen-dependently with peptide-major histocompatibility complex...