A5015522784- Immunotherapy and Immune Responses
- Heat shock proteins research
- vaccines and immunoinformatics approaches
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Hepatitis B Virus Studies
- Endoplasmic Reticulum Stress and Disease
- Cancer Immunotherapy and Biomarkers
- Toxin Mechanisms and Immunotoxins
- T-cell and B-cell Immunology
- thermodynamics and calorimetric analyses
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Cancer, Stress, Anesthesia, and Immune Response
- Escherichia coli research studies
- Cancer Research and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Immune cells in cancer
- Vector-borne infectious diseases
- Pharmacogenetics and Drug Metabolism
- Bladder and Urothelial Cancer Treatments
- Metabolism and Genetic Disorders
University of Connecticut
2015-2025
Universidad Cristiana Autónoma de Nicaragua
2024
UConn Health
2008-2023
Banaras Hindu University
1996-2022
Washington State University Spokane
2018
U-M Rogel Cancer Center
2013-2017
Farmington Community Library
2013-2015
Comprehensive Blood & Cancer Center
2014
University of Washington
2014
Plant & Food Research
2014
Dendritic cells (DC) are key components of innate and adaptive immune responses. The identity endogenous signals that activate DC is a crucial unresolved question. We report here heat shock proteins (HSP), the most abundant conserved mammalian molecules, constitute such an internal signal. Necrotic but not apoptotic cell death leads to release HSP gp96, calreticulin, hsp90 hsp70. stimulate macrophages secrete cytokines, induce expression antigen-presenting co-stimulatory molecules on DC....
Endogenously synthesized antigenic determinants are generally presented on major histocompatibility complex (MHC) class I molecules, whereas exogenous by MHC II molecules. Here, it is shown that antigens chaperoned a heat shock protein can be channeled into the endogenous pathway, and recognized CD8 + T lymphocytes. This pathway functional only in subset of macrophages among cell types tested. These observations provide basis for tumor-specific virus-specific immunogenicity cognate...
Immunotherapy of mice with preexisting cancers heat shock protein preparations derived from autologous cancer resulted in retarded progression the primary cancer, a reduced metastatic load, and prolongation life-span. Treatment other than did not provide significant protection. Spontaneous (lung melanoma), chemically induced (fibrosarcoma colon carcinoma), an ultraviolet radiation-induced spindle cell carcinoma were tested, results support efficacy cancer-derived protein-peptide complexes...
Vaccination of mice with heat shock protein 70 (hsp70) preparations derived from the Meth A sarcoma, but not normal tissues, renders immune to a substantial challenge sarcoma. The immunogenicity is dose dependent and tumor specific. Treatment an antigenically active hsp70 preparation ATP followed by removal low-molecular weight material leaves intact, as judged SDS-PAGE results in loss antigenicity, rejection assays. Separation this on C18 reverse-phase column shows diverse array peptides...
Heat shock protein (HSP) preparations derived from cancer cells and virus-infected have been shown previously to elicit cancer-specific or virus-specific immunity. The immunogenicity of HSP has attributed peptides associated with the HSPs. studies reported here demonstrate that immunogenic HSP-peptide complexes can also be reconstituted in vitro. show (a) hsp70 gp96 molecules a variety synthetic generated vitro; (b) binding HSPs is specific number other proteins tested do not bind under...
Chemically induced sarcomas of inbred mice are immunogenic in syngeneic hosts, and preimmunization with tumor cells leads to resistance subsequent transplants. The rejection antigens (TRAs) that mediate this reaction highly specific for each tumor; cross-protection between different is rare. Isolated membrane cytosol fractions from two antigenically distinct BALB/c sarcomas, Meth A CMS5, have TRA activity, biochemical characterization the active components plasma membranes these tumors...
Stress-induced proteins (or heat shock (HSPs)) of 96 kDa size (gp96) have been shown previously to elicit specific immunity tumors from which they are isolated. In this report, we show that in contrast Meth A-derived gp96, gp96 preparations derived normal tissues did not A sarcoma at any dose tested. Further, light recent studies showing other major cellular HSPs hsp90 and hsp70 also tumor-specific immunity, compared the relative immunogenicities hsp90, sarcoma. The were observed be highly...
PURPOSE: To determine the immunogenicity and antitumor activity of a vaccine consisting autologous, tumor-derived heat shock protein gp96-peptide complexes (HSPPC-96, Oncophage; Antigenics, Inc, Woburn, MA) in metastatic (American Joint Committee on Cancer stage IV) melanoma patients. PATIENTS AND METHODS: Sixty-four patients had surgical resection tissue required for production, 42 were able to receive vaccine, 39 assessable after one cycle vaccination (four weekly injections). In 21...
The mutational repertoire of cancers creates the neoepitopes that make immunogenic. Here, we introduce two novel tools identify, with relatively high accuracy, small proportion (among hundreds potential neoepitopes) protect host through an antitumor T cell response. consist (a) numerical difference in NetMHC scores between mutated sequences and their unmutated counterparts, termed differential agretopic index, (b) conformational stability MHC I–peptide interaction. Mechanistically, these...
T cells recognize neoepitope peptide-major histocompatibility complex class I on cancer cells. The strength (or avidity) of the cell receptor–peptide-major interaction is a critical variable in immune control cancers. Here, we analyze neoepitope-specific CD8 distinct avidities and show that low-avidity are sole mediators mice solely responsive to checkpoint blockade humans. High-avidity ineffective immune-suppressive. mechanistic basis these differences lies higher exhaustion status...
Purified preparations of 96-kDa heat shock proteins (gp96) have been previously shown to elicit tumor-specific immunity the tumor from which gp96 is obtained but not antigenically distinct chemically induced tumors. The cellular requirements gp96-elicited examined. It observed that depletion CD8+, CD4+, T cells in priming phase abrogates elicited by gp96. CD8+ immunization with are active at least up 5 weeks after immunization. Depletion macrophages treatment mice carrageenan during also...
Abstract Upon exposure to lysates or supernatants of necrotic transformed cell lines, human dendritic cells (DCs) undergo maturation. In contrast, DCs exposed apoptotic lines primary remain immature. Analysis showed them be enriched in the heat shock proteins (hsp)70 and gp96, contrast cells. Likewise, from a variety tumors contained considerably higher levels hsp than their normal autologous tissue counterparts. Of majority hsps (hsp70 and/or gp96), corresponding matured DCs. The maturation...
Abstract NO is a cytotoxic and immunomodulatory cytokine produced by macrophages dendritic cells. We show that stimulation of murine human with the heat shock proteins gp96 hsp70 results in induction inducible synthase production NO. The release monocytes exposed to hsp60 has been documented previously. Immature, but not mature, cells respond same manner. activity relatively unaffected an antagonist LPS, abrogated denaturation. Macrophages have shown previously produce response IFN-γ;...