| Mechanisms Underlying the Breast Cancer Susceptibility Locus Mcs5a |
Jul-2009 |
15 pages |
| Authors:
Bart M Smits; WISCONSIN UNIV-MADISON
|
 | For low-penetrance breast cancer risk alleles it is currently unknown how they lead to predisposition. Here, we study the Mcs5a locus that is associated with breast cancer risk in rats and humans. In our rat model we show that the presence of the resistant genotype of two components of the locus (Mcs5a1, Mcs5a2) down regulates the expression of the Fbxo10 gene in the T cells and that this reduced expression ... |
|
| Enhancement of Dendritic Cell-Based Immunotherapy Using a Small Molecule TGF-beta Receptor Type I Kinase Inhibitor |
Jul-2009 |
31 pages |
| Authors:
Matthew Rausch; ARIZONA UNIV TUCSON
|
| Dendritic cells (DC) have become particularly attractive candidates for cancer immunotherapy due to their potent ability to stimulate antigen specific T cells responses. To date DC-based immunotherapy has demonstrated only limited clinical success in the treatment of established tumors. The limited clinical efficacy of existing DC-based cancer vaccines has been attributed in part to suppressive factors produced by the growing tumor, such as transforming growth factor-beta (TGF-beta) that has been ... |
|
| Enhanced Eradication of Lymphoma by Tumor-Specific Cytotoxic T Cells Secreting and Engineered Tumor-Specific Immunotoxin |
Jun-2009 |
11 pages |
| Authors:
Patricia Yotnda; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| In this project, we proposed to use tumor-specific T cells to produce an immunotoxin (IT) targeting tumor cells only when these T cells are specifically activated by the tumor. We use lentiviral vectors to modify tumor specific T cells with our immunotoxin. PEA based immunotoxins affect cell viability by ADP ribozilation of their elongation factor-2. To produce high titer of vector encoding the IT we generated a producer cell line ... |
|
| Regulatory T Cells and Host Anti-CML Responses |
Jun-2009 |
9 pages |
| Authors:
Wong; K K Jr; CITY OF HOPE BECKMAN RESEARCH INST DUARTE CA
|
| CD4+CD25+FoxP-3+ regulatory T-cells (Tregs) suppress immune responses to 'self' antigens, but also have been shown to suppress host anti-tumor responses in several human malignancies, including breast, gastrointestinal, and ovarian cancer. Identification of CML Tregs as suppressors of host anti-CML responses could have a significant impact upon CML treatment strategies. Methods are currently available to selectively suppress Tregs and subsequently boost host anti-CML responses. We have examined the CD4+CD25+FoxP-3+ regulatory T-cell ... |
|
| Enhancing the Efficacy of Dendritic Cell Vaccines by Tissue Conditioning |
Mar-2009 |
10 pages |
| Authors:
Philipp Dahm; FLORIDA UNIV GAINESVILLE
|
| The overall objective of this proposal has been to investigate the novel in situ immune modulation for enhancing the efficacy of cancer vaccines. The central hypothesis of the approach under investigation is that the ex vivo step of DC maturation as a necessary prerequisite for generating migratory DC capable of stimulating strong antigen-specific T cell responses can be replaced by an in vivo process termed in situ priming. Based on ... |
|
| Identification and Characterization of Ovarian Carcinoma Peptide Epitopes Recognized by Cylotoxic T Lymphocytes |
Nov-2008 |
75 pages |
| Authors:
Kevin T Hogan; VIRGINIA UNIV CHARLOTTESVILLE
|
| The purpose of the research was to identify new ovarian cancer tumor antigens that could be used in the development of an ovarian cancer vaccine. The scope of the work involved identifying peptide antigens recognized by ovarian cancer reactive cytotoxic T lymphocytes (CTL). Eleven ovarian cancer cell lines were characterized for their expression of tumor antigens and MHC molecules This was significant because it provided a resource that could be ... |
|
| Enhancing Anti-Breast Cancer Immunity by Blocking Death Receptor DR5 |
Sep-2008 |
18 pages |
| Authors:
Wei-Zen Wei; WAYNE STATE UNIV DETROIT MI
|
| The original hypothesis was that blocking DR5 with vaccine-induced antagonist antibodies (Ab) will protect T cells from TRAIL-induced apoptosis and enhance their anti-tumor activity. The three specific aims were to (1) Construct and test DR5 vaccines to induce anti-DR5 Ab (2) Test the antagonist activity of vaccine-induced anti-DR5 Ab and (3) Amplify anti-tumor immunity by DR5 vaccination. We found that immune sera to human DR5 showed significant agonist rather than ... |
|
| Mechanisms Underlying the Breast Cancer Susceptibility Locus Mcs5a |
Jul-2008 |
13 pages |
| Authors:
Bart M Smits; WISCONSIN UNIV-MADISON
|
| For low-penetrance breast cancer risk alleles it is currently unknown how they lead to predisposition. Here, we study the Mcs5a locus that is associated with breast cancer risk in rats and humans. In our rat model we show that the presence of the resistant genotype of two components of the locus (Mcs5a1, Mcs5a2) down regulates the expression of the Fbxo10 gene in the T cells and that this reduced expression ... |
|
| Regulatory T Cells and Host Anti-CML Responses |
01-Jun-2008 |
9 pages |
| Authors:
Wong; K K Jr; CITY OF HOPE NATIONAL MEDICAL CENTER DUARTE CA
|
| CD4+CD25+FoxP-3+ regulatory T-cells (Tregs) suppress immune responses to "self" antigens, but also have been shown to suppress host anti-tumor responses in several human malignancies, including breast, gastrointestinal, and ovarian cancer. Identification of CML Tregs as suppressors of host anti-CML responses could have a significant impact upon CML treatment strategies. Methods are currently available to selectively suppress Tregs, and subsequently boost host anti-CML responses. We have examined the CD4+CD25+FoxP-3+ regulatory T-cell ... |
|
| Development of Augmented Leukemia/Lymphoma-Specific T-Cell Immunotherapy for Deployment with Haploidentical, Hematompoietic Progenitor-Cell Transplant |
01-May-2008 |
33 pages |
| Authors:
Laurence Cooper; Rita Young; M D ANDERSON CANCER CENTER HOUSTON TX
|
| To develop T-cell therapies for B-cell malignancies we have developed a chimeric antigen receptor (CAR) which when expressed on the cell surface redirects T-cell specificity for CD19, a B-lineage cell-surface antigen. We have undertaken a series of systematic experiments to improve the ability of these CAR+ T cells to persist after adoptive transfer based on conditional expression of interleukin-2 (IL-2) which is a potent cytokine that can prolong T-cell persistence. ... |
|
| A Direct Synergistic Effect of Immunotherapy and Chemotherapy as a New Paradigm in Treatment of Breast Cancer |
APR 2008 |
10 pages |
| Authors:
Dmitry Gabrilovich; H LEE MOFFITT CANCER CENTER AND RESEARCH INST TAMPA FL
|
| Treatment of patients with advanced stages of breast cancer remains an unresolved clinical problem. The main objectives of this study are to determine whether immunotherapy sensitizes tumor to chemotherapy and to identify some of the main mechanisms of this effect. We investigated the possibility of a direct synergy between immunotherapy and chemotherapy in vitro. We found that pre-treatment of tumor target cells with doxorubicin or paclitaxel significantly increased cytotoxic effect ... |
|
| Functional CD8+ T Cell Responses in Lethal Ebola Virus Infection |
15 MAR 2008 |
10 pages |
| Authors:
Steven B. Bradfute; Kelly L. Warfield; Sina Bavari; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Ebolavirus (EBOV) causes highly lethal hemorrhagic fever that leads to death in up to 90% of infected humans. EBOV infection induces massive lymphocyte apoptosis, which is thought to prevent a functional adaptive immune response. In addition, in vitro studies show that EBOV induces aberrant responses in dendritic cells, which is thought to contribute to a failed adaptive immune response. In this study we show that in a lethal mouse model ... |
|
| Innate Anti-Breast Cancer Activity of (Gamma)/(Delta) T-Cells: A Novel Biological and Clinical Approach to the Treatment of Relapsed or Refractory Breast Cancer |
01-Mar-2008 |
6 pages |
| Authors:
Richard D Lopez; ALABAMA UNIV IN BIRMINGHAM
|
| We initially identified and characterized a CD2-mediated interleukin (IL)-12-dependent signaling pathway which inhibits apoptosis in mitogen-stimulated human -T cells. We have since exploited this pathway to develop the methodologies allowing the large-scale ex vivo expansion of viable apoptosis-resistant -T cells - an undertaking until now not possible. Importantly we have shown that apoptosis- resistant human -T cells retain significant innate major histocompatibility complex (MHC)-unrestricted cytotoxicity against a wide variety of ... |
|
| Phenotype and Function of Bone Marrow Infiltrating Lymphocytes in Chronic Myelogenous Leukemia |
01-Feb-2008 |
31 pages |
| Authors:
Vinod Pullarkat; CITY OF HOPE DUARTE CA
|
| The aims of this project are to determine the phenotype and antileukemic activity of activated bone marrow infiltrating leukemia (MIL) and compare them to activated peripheral blood lymphocytes from patients with chronic myelogenous leukemia (CML) on imatinib or other tyrosine kinase inhibitor therapy. Bone marrow and peripheral blood specimens were obtained from CML patients who had at least a minor cytogenetic response. The phenotype of MILs and peripheral blood lymphocytes ... |
|
| Dendritic Cell-Based Genetic Immunotherapy for Ovarian Cancer |
Dec-2007 |
73 pages |
| Authors:
James M Mathis; LOUISIANA STATE UNIV IN SHREVEPORT
|
| Adenovirus (Ad)-mediated transduction of dendritic cells (DCs) is inefficient because of the lack of the primary Ad receptor, CAR. CD40 is a surface marker expressed by DCs that plays a crucial role in their maturation and subsequent stimulation of T cells. DC infection with Ad targeted to the CD40 results in increased gene transfer. Cells transduced with CD40-targeted Ad5-SV40-TAg vector showed increased expression of transgene and expression of co-stimulatory molecules ... |
|
| Enhancement of Anti-Telomerase Immunity Against Prostate Cancer |
01-Nov-2007 |
48 pages |
| Authors:
Johannes Vieweg; DUKE UNIV MEDICAL CENTER DURHAM NC
|
| The major objective of this proposal is to enhance the efficacy of specific active immunotherapy (SAI) by selectively eliminating or reducing CD4+ regulatory T cells (T(sub reg))1 in patients with metastatic prostate cancer. Preclinical and clinical data from our laboratory have shown that CD4+ and CD25+ co-expressing T(sub reg) play an important role in the suppression of T cell responses in the cancer patient. Moreover, we have demonstrated that elimination ... |
|
| Prostate Derived Ets Factor, An Immunogenic Breast Cancer Antigen |
SEP 2007 |
9 pages |
| Authors:
Ashwani Sood; ROSWELL PARK CANCER INST BUFFALO NY
|
| The goal of the proposed research was to test the following concept: Due to the prostate restricted expression of Pse in normal tissues of mice Pse is likely to be immunogenic in female mice. T cell responses of male and female mice to Pse and a control antigen Her2lneu were compared. Two different assays were used for this purpose; the ELlspot assay and the Cytotoxicity assay. We found that in ... |
|
| Role of the Tyrosine Phosphatase SHP-1 and Regulatory T Cells in Breast Cancer |
Sep-2007 |
8 pages |
| Authors:
Ulrike Lorenz; VIRGINIA UNIV CHARLOTTESVILLE
|
| Uncontrolled proliferation of tumor cells due to failure of immune-surveillance has been linked to cancer development. Regulatory T cells (Treg) play a critical role in immune tolerance by suppressing immune responses to the body's own antigens. The tyrosine phosphatase SHP-1 is a well-known negative regulator of T cell signaling that also affects the generation of Treg cells. Interestingly, mice with decreased levels of SHP-1 protein show a high occurrence of ... |
|
| Broad T Cell Immunity to the LcrV Virulence Protein is Induced by Targeted Delivery to DEC-205/CD205-Positive Mouse Dendritic Cells |
13 AUG 2007 |
11 pages |
| Authors:
Yoonkyung Do; Chae Gyu Park; Young-Sun Kang; Sung Ho Park; Rebecca M. Lynch; Haekyung Lee; Bradford S. Powell; Ralph M. Steinman; ROCKEFELLER UNIV NEW YORK
|
| There is a need for a more efficient vaccine against the bacterium Yersinia pestis, the agent of pneumonic plague. The F1-LcrV (F1-V) subunit vaccine in alhydrogel is known to induce humoral immunity. In this study, we utilized DC to investigate cellular immunity. We genetically engineered the LcrV virulence protein into the anti-DEC-205 CD205 mAb and thereby targeted the conjugated protein directly to mouse DEC205+ DC in situ. We observed antigen-specific ... |
|
| Trials of Anti-PSMA Designer T Cells in Advanced Prostate Cancer (Phase 1). Revision |
JUL 2007 |
9 pages |
| Authors:
Richard P. Junghans; ROGER WILLIAMS MEDICAL CENTER PROVIDENCE RI
|
| Anti-PSMA designer T cells Autologous T cells that are gene-modified to express chimeric immunoglobulin T cell receptors (TgTCR) that recognize the prostate specific membrane antigen. We will conduct Phase I dose-escalation trial with infusion of designer T cells into prostate cancer patients after non-myeloablative (NMA) conditioning. This procedure will allow for the stable engraftment and persistence of the infused cells for improved therapeutic effect. The first year efforts have been ... |
|
| Development of Artificial Antigen Presenting Cells for Prostate Cancer Immunotherapy |
MAY 2007 |
10 pages |
| Authors:
Jonathan P. Schneck; Mathias Oelke; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
|
| While adoptive immunotherapy holds promise as a treatment for cancer, development of adoptive immunotherapy has been impeded by the lack of a reproducible and economically viable method for generating therapeutic numbers of antigen-specific CTL. The issues of reproducibility and cost, in large part, relate to the use of cellular dendritic cells (DC) for expansion of CTL. Underlying disease and pretreatment often affect the number of and efficacy of DC. Induction ... |
|
| Homeostatic T Cell Expansion to Induce Anti-Tumor Autoimmunity in Breast Cancer |
01 APR 2007 |
21 pages |
| Authors:
Roberto Baccala; SCRIPPS RESEARCH INST LA JOLLA CA
|
| We have previously shown that effective anti-tumor autoimmunity can be induced if a tumor-cell challenge is given to mice undergoing homeostatic T-cell proliferation, a process dependent on signaling by self-peptide/MHC and trophic cytokines. We investigated whether this principle can be applied to mouse models of advanced breast carcinoma, and whether the anti-tumor response can be enhanced using selected T-cell subpopulations, cytokines and tumorvaccines. The results indicated that (a) homeostatic T-cell ... |
|
| Phenotype and Function of Bone Marrow Infiltrating Lymphocytes in Chronic Myelogenous Leukemia |
APR 2007 |
8 pages |
| Authors:
Vinod Pullarkat; CITY OF HOPE DUARTE CA
|
| The aims of this project are to determine the phenotype and antileukemic activity of activated bone marrow infiltrating leukemia (MIL) and compare them to activated peripheral blood lymphocytes from patients with chronic myelogenous leukemia (CML) on imatinib or other tyrosine kinase inhibitor therapy. Bone marrow and peripheral blood specimens were obtained from CML patients who had at least a minor cytogenetic response. The phenotype of MILs and peripheral blood lymphocytes ... |
|
| The Influences of Glycosylation on the Antigenicity, Immunogenicity, and Protective Efficacy of Ebola Virus GP DNA Vaccines |
22 NOV 2006 |
19 pages |
| Authors:
William Dowling; Elizabeth Thompson; Catherine Badger; Jenny L. Mellquist; Aura R. Garrison; Jeffrey M. Smith; Jason Paragas; Robert J. Hogan; Connie Schmaljohn; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| The Ebola virus (EBOV) envelope glycoprotein (GP) is the primary target of protective immunity. Mature GP consists of two disulfide-linked subunits, GP1 and membrane-bound GP2. GP is highly glycosylated with both N- and O-linked carbohydrates. We measured the influences of GP glycosylation on antigenicity, immunogenicity, and protection by testing DNA vaccines comprised of GP genes with deleted N-linked glycosylation sites or with deletions in the central hypervariable mucin region. We ... |
|
| Enhancement of Anti-Telomerase Immunity Against Prostate Cancer |
NOV 2006 |
18 pages |
| Authors:
Johannes Vieweg; DUKE UNIV MEDICAL CENTER DURHAM NC
|
| The overall objective of this proposal is to enhance the efficacy of cancer vaccines by selectively eliminating or reducing CD4+ regulatory T cells (Treg) expressing the high affinity CD25 IL-2-specific receptor (IL-2R) in patients with metastatic prostate cancer. Preclinical and clinical data from our laboratory (see Reference 1 and Appendix A) and others (2, 3) have shown that CD4+/CD25+ Treg play an important role in the suppression of T cell ... |
|
| Identification and Characterization of Ovarian Carcinoma Peptide Epitopes Recognized by Cytotoxic T Lymphocytes |
NOV 2006 |
43 pages |
| Authors:
Kevin T. Hogan; VIRGINIA UNIV CHARLOTTESVILLE
|
| The purpose of the research is to identify new ovarian cancer tumor antigens that can be used in the immunotherapeutic treatment of ovarian cancer. The scope of this work involves (1) identifying the peptide antigens recognized by ovarian reactive cytotoxic T lymphocytes (CTL) by using an antigen-unbiased mass spectrometric approach to antigen identification; and (2) identify peptide antigens within the Her-2/neu folate binding protein (FBP) and TAG proteins that give ... |
|
| Bone Marrow Function in Development of Childhood Asthma |
OCT 2006 |
22 pages |
| Authors:
Mary B. Hogan; WEST VIRGINIA UNIV RESEARCH CORP MORGANTOWN
|
| Asthma is the most common reason for hospitalization of children in military hospitals. In children with asthma, exposure to allergen results in pulmonary damage due to invasion of eosinophils. Eosinophils are inflammatory cells with limited life spans, and must be continually renewed from the bone marrow. We adapted an animal model of asthma to study the effect of allergen exposure on eosinophil progenitor cells (CFU-eo). These studies have revealed that ... |
|
| Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer |
JUL 2006 |
18 pages |
| Authors:
Donald W. Kufe; DANA-FARBER CANCER INST BOSTON MA
|
| The overall objective of this project is to study the safety, immunologic response and clinical effects of vaccinating breast cancer patients with dendritic cell (DC)/tumor fusions in conjunction with IL-12. Studies performed in Task 1 have shown that the DC/breast tumor fusions are effective in (1) stimulating cytokine production, and (2) inducing tumor-specific T cell responses. Work performed over the past year has extended these studies by further defining the ... |
|
| The Bacterial Gene IfpA Influences the Potent Induction of Calcitonin Receptor and Osteoclast-Related Genes in Burkholderia Pseudomallei-Induced TRAP-Positive Multinucleated Giant Cells |
13 JUN 2006 |
20 pages |
| Authors:
Justin A. Boddey; Christopher J. Day; Cameron P. Flegg; Ricky L. Ulrich; Sebastien R. Stephens; Ifor R. Beacham; Nigel A. Morrison; Ian R. Peak; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Burkholderia pseudomallei is a facultative intracellular pathogen and the causative agent of melioidosis, a spectrum of potentially fatal diseases endemic in Northern Australia and South-East Asia. We demonstrate that B. pseudomallei rapidly modifies infected macrophage-like cells in a manner analagous to osteoclastogenesis. These alterations include multinucleation and the expression by infected cells of mRNA for factors required for osteoclastogenesis: the chemokines monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1 ... |
|
| A Fusogenic Oncolytic Herpes Simplex Virus for Therapy of Advanced Ovarian Cancer |
JUN 2006 |
9 pages |
| Authors:
Xiaoliu Zhang; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| For efficient therapy of solid tumors such as ovarian cancer, two obstacles need to be overcome before the therapeutic potential of virotherapy could be fully materialized. Firstly, the potency of oncolytic HSVs needs to be improved. During the first two years of this funded project, we have demonstrated that incorporation of cell-membrane fusion activity into an oncolytic HSV could significantly and safely increase the antitumor potency of the virus. Secondly, ... |
|
| Selective Inhibition of T Cell Tolerance as a Means of Enhancing Tumor Vaccines in a Mouse Model of Breast Cancer |
JUN 2006 |
8 pages |
| Authors:
Jonathan Powell; JOHNS HOPKINS UNIV BALTIMORE MD
|
| To determine if the addition of Go6976 to vaccine protocols will inhibit neu specific tolerance and enhance immunotherapy for breast cancer. Scope: In the Her-2/neu model of spontaneous breast cancer the immune system of these transgenic mice are tolerant to the neu protein. While immunity to neu can be demonstrated in the neu-transgenic mice (partial breaking of tolerance), this immunity is inadequate to prevent the spontaneous development of tumors and ... |
|
| Spatial-Temporal Mapping of the T Cell Receptor NF-kappaB Signaling Pathway |
30 MAY 2006 |
131 pages |
| Authors:
Jeremy S. Rossman; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF MICROBIOLOGY AND IMMUNOLOGY
|
| T lymphocytes are critical mediators of adaptive immunity that recognize antigen through the T cell receptor (TCR). Stimulation of the TCR leads to a complex signal transduction cascade resulting in the activation of the transcription factors NFAT, AP-1 and NF-kappaB. The activation of these transcription factors is a crucial step in T lymphocyte activation. TCR stimulation results in the spatial redistribution of several proteins involved in signal transduction to NF-kappaB. ... |
|
| The T Cell Response to Actinobacillus actinomycetemcomitans |
MAY 2006 |
90 pages |
| Authors:
Patrick M. McDonough; TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO GRADUATE SCHOOL OF BIOMEDICAL SCIENCES
|
| The association between Actinobacillus actinomycetemcomitans (Aa) and aggressive periodontitis is well documented. Although the humoral immune response to Aa has been thoroughly studied, little is known concerning the Aa proteins that elicit a T cell response. Heat shock proteins (HSPs) are known to be immunodominant in some oral and non-oral diseases. The purpose of our study was to characterize more fully the T cell response to the Aa HSPs GroEL, ... |
|
| Secondary Lymphoid Tissue Chemokine as an Immunotherapeutic Against Primary and Metastatic Breast Cancer |
MAY 2006 |
11 pages |
| Authors:
Abdelkader Ashour; Heth R. Turnquist; NEBRASKA UNIV MEDICAL CENTER OMAHA
|
| T cells dendritic cells (DOs) and natural killer (NK) cells are known to be involved in anti-tumor immune responses. These cell types all express a common receptor CCR7 which binds the chemokine secondary lymphoid chemokine (SLC also called CCL21). In Task 1 we examined the effect of SLC/CCL21 administered via a sustained delivery system in a mouse breast cancer model that mirrors the progress of human breast cancer. Utilizing this ... |
|
| Novel MHC Class II Breast Cancer Vaccine Using RNA Interference (RNAi) to Down Regulate Invariant Chain (li) |
MAY 2006 |
42 pages |
| Authors:
James A. Thompson; MARYLAND UNIV BALTIMORE COUNTY BALTIMORE MD
|
| Our goal is to induce a strong CD4+ T cell response against tumor antigens by preferentially presenting endogenous tumor antigens via class II major histocompatibility complex molecules (MHC II). MHC II can present endogenous tumor antigens if expressed in the absence of Invariant chain (Ii). We have up-regulated MHCII and down regulated Ii without affecting MHC II expression in tumor cells. Using the key transcription factor class II trans-activator (CIITA) ... |
|
| Homeostatic T Cell Expansion to Induce Anti-Tumor Autoimmunity in Breast Cancer |
APR 2006 |
12 pages |
| Authors:
Roberto Baccala; SCRIPPS RESEARCH INST LA JOLLA CA
|
| In previous studies, we have shown that effective anti-tumor autoimmunity can be elicited if a tumorcell challenge is given in conjunction with homeostatic T-cell proliferation, a process occurring in response to lymphopenia and dependent on signaling by self-peptide/MHC and trophic cytokines. We are currently investigating whether this principle can be applied to mouse models of advanced breast carcinoma, and whether the anti-tumor response can be enhanced using selected T-cell subpopulations, ... |
|
| Exploiting the Innate Antitumor Activity of Human gammadelta-TCells for the Treatment of Prostate Cancer |
APR 2006 |
28 pages |
| Authors:
Richard Lopez; ALABAMA UNIV IN BIRMINGHAM
|
| We initially identified a CD2-mediated, interleukin (IL)-12 dependent signaling pathway which inhibits apoptosis in mitogen-stimulated human gamma/delta T-cells. We have since exploited this pathway to develop the methodologies allowing the large-scale ex vivo expansion of viable apoptosis-resistant - T cells. We have shown that apoptosis-resistant human T- cells retain significant innate, major histocompatibility complex (MHC)-unrestricted cytotoxicity against human prostate cancer cell lines. Purpose and scope: The aims of this project ... |
|
| Rescuing High Avidity T Cells for Prostate Cancer Immunotherapy |
APR 2006 |
67 pages |
| Authors:
Pan Zheng; OHIO STATE UNIV COLUMBUS
|
| This is the final report on the grant Rescuing high avidity T cells for prostate cancer immunotherapy. The purpose of the grant proposal is to rescuing high avidity tumor-antigen specific T cells that can respond effectively to prostate cancer cells and delay the development of prostate cancer in the TRAMP mouse model. We have proposed three specific aims. (1). Identify the cells in thymus that express peripheral tumor antigen to ... |
|
| Human CD1d-Restricted Natural Killer T (NKT) Cell Cytotoxicity Against Myeloid Cells |
APR 2006 |
56 pages |
| Authors:
Xiuxu Chen; Jenny E. Gumperz; WISCONSIN UNIV-MADISON
|
| CD1d-restricted natural killer T cells (NKT cells) are a unique subpopulation of T lymphocytes that have been shown to be able to promote potent anti-tumor responses in a number of different murine (mouse) cancer models, Little is known about whether they may play a role in preventing or controlling human cancers and in particular there is little information about whether they can function to kill cancer cells as they arise ... |
|
| Consequences of Cyclin D1/BRCA1 Interaction in Breast Cancer Progression |
APR 2006 |
33 pages |
| Authors:
Kylene Kehn; Fatah Kashanchi; Maria E. Bottazzi; GEORGE WASHINGTON UNIV WASHINGTON DC
|
| The inheritance of one defective BRCA1 or BRCA2 allele predisposes an individual to developing breast, ovarian and T-cell cancers. In addition, in breast cancers where BRCA1 is not mutated, it is often functionally inactivated. Furthermore, cyclin D1 has been shown to be overexpressed in many cancers including breast cancer and its associates with BRCA1. Because of the crucial role of both of these proteins in cancer, it is reasonable to ... |
|
| Enhancing Anti-Prostate Cancer Immunity Through OX40 Engagement |
FEB 2006 |
10 pages |
| Authors:
Andrew D. Weinberg; PROVIDENCE HEALTH SYSTEMS-OREGON PORTLAND
|
| The goal of the proposed studies is to extend our OX40-specific anti-tumor responses to prostate tumor models by using a protein found on the surface of the T helper subset of leukocytes (OX40). Anti-OX40 delivered into animals with ongoing immune responses are able to clear the tumors and pathogens quicker following the acute immune response and also are left with a greater amount of immunologic memory . The greater number ... |
|
| Treatment of Mestastatic Breast Cancer by Photodynamic Therapy Induced Anti-Tumor Immunity in a Murine Model |
DEC 2005 |
13 pages |
| Authors:
Ana P. Castano; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| One in 8 women in the United States will develop breast cancer during her lifetime. Deaths are due to tumors that have metastasized. Photodynamic therapy (PDT) is a promising cancer treatment in which a photosensitizer (PS) accumulates in tumors and is subsequently activated by visible light of an appropriate wavelength. PDT produces cell death and tumor ablation. Mechanisms include cytotoxicity to tumor cells, shutting down of the tumor vasculature, and ... |
|
| Tumor Vaccination With Cytokine-Loaded Microspheres |
DEC 2005 |
29 pages |
| Authors:
Nejat K. Egilmez; LOUISVILLE UNIV KY
|
| A single intra-tumoral injection of IL-12 + GM-CSF-encapsulated microspheres promoted the suppression of primary tumor growth prevented the development of additional tumors and extended survival in the her2-neu transgenic FVB/neuN murine mammary tumor model. Induction of a long-lived systemic tumor-specific immune response was demonstrated in adoptive cell transfer studies cytotoxic T-cell assays in vivo lymphocyte subset depletion studies and analysis of serum anti-tumor antibody levels. Repeated treatment was more effective ... |
|
| Enhancement of Anti-Telomerase Immunity Against Prostate Cancer |
NOV 2005 |
19 pages |
| Authors:
Johannes W. Vieweg; DUKE UNIV MEDICAL CENTER DURHAM NC
|
| The overall objective of this proposal is to enhance the efficacy of cancer vaccines by selectively eliminating or reducing CD4+ regulatory T cells (Treg) expressing the high affinity CD25 IL-2-specific receptor (IL-2R) in patients with metastatic prostate cancer. Preclinical and clinical data from our laboratory and others have shown that CD4+/CD25+ Treg play an important role in the suppression of T cell responses and that elimination of Treg is capable ... |
|
| Identification and Characterization of Ovarian Carcinoma Peptide Epitopes Recognized by Cylotoxic T Lymphocytes |
NOV 2005 |
17 pages |
| Authors:
Kevin T. Hogan; VIRGINIA UNIV CHARLOTTESVILLE
|
| The purpose of the research is to identify new ovarian cancer tumor antigens that can be used in the immunotherapeutic treatment of ovarian cancer. The scope of this work involves (1) identifying the peptide antigens recognized by ovarian reactive cytotoxic T lymphocytes (CTL) by using an antigen-unbiased, mass spectrometric approach to antigen identification; and (2) identify peptide antigens within the Her-2/neu, folate binding protein (FBP), and TAG proteins that give ... |
|
| Monitoring Cellular Interactions during T Cell Activation at the Single Molecule Level Using Semiconductor Quantum-Dots |
05 OCT 2005 |
8 pages |
| Authors:
Shimon Weiss; Owen Witte; Laurent Bentolila; Fabien Pinaud; James Tsay; Caius Radu; Lili Wang; CALIFORNIA UNIV LOS ANGELES DEPT OF CHEMISTRY AND BIOCHEMISTRY
|
| Enhanced peptide-coated quantum dots (with high brightness and high saturation intensity) were developed. Two high-affinity targeting "velcro-pairs" based on avidin-biotin and fluorescine-antibody interactions were demonstrated and used to specifically target single proteins in membranes of live cells. Single molecule spectroscopy and imaging of individual quantum dot-labeled lipid rafts receptors were performed. Software tools were developed to analyze individual diffusion and trafficking trajectories. These studies provide strong support for the lipid ... |
|
| Cytolytic T Lymphocytes in Organotypic Breast Carcinoma Culture |
OCT 2005 |
12 pages |
| Authors:
Dorothee Herlyn; PENNSYLVANIA UNIV PHILADELPHIA WISTAR INST
|
| In the proposed studies, novel T cell immunotherapies against breast cancer will be developed based on studies demonstrating a positive correlation between T lymphocytic infiltration of these tumors and favorable clinical outcome. The major goal of the proposed studies is to isolate and characterize cytolytic T lymphocytes (CTL) with in vivo-like T cell receptors. The CTL provide the basis for adoptive CTL immunotherapy and active immunotherapy with CTtderived peptides/antigens. During ... |
|
| Persistence of Zinc-Binding Bacterial Superantigens at the Surface of Antigen-Presenting Cells Contributes to the Extreme Potency of These Superantigens as T-Cell Activators |
SEP 2005 |
10 pages |
| Authors:
Dorothy D. Pless; Gordon Ruthel; Emily K. Reinke; Robert G. Ulrich; Sina Bavari; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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| Bacterial superantigen intoxication causes massive overactivation of T cells, which can result in potentially lethal toxic shock. Superantigens fall into two groups: superantigens such as staphylococcal enterotoxin B (SEB) that contain a single generic binding site for major histocompatibility complex class II (MHC-II) and more potent superantigens such as SEA with a second, zinc-dependent MHC-II binding site that enables them to cross-link adjacent MHC-II molecules. We found that although all ... |
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| Maximizing Immune Response to Carbohydrate Antigens on Breast Tumors |
AUG 2005 |
70 pages |
| Authors:
Thomas Kieber-Emmons; ARKANSAS UNIV FOR MEDICAL SCIENCES LITTLE ROCK
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| Future progress to improve the overall survival of breast cancer patients will depend on introducing new therapies such as cancer vaccines. Because the majority of cell proteins and lipids are glycosylated, tumor associated carbohydrate antigens (TACA) are attractive as potential targets for cancer vaccines. However, tumor-associated carbohydrate antigens are both T-cell-independent antigens and self-antigens, impacting on their ability to induce generate strong, sustained responses against these antigens. To maximize tumor- ... |
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| Regulation of T-Type Cyclin/CDK9 Complexes in Breast Cancer Cells |
01 JUL 2005 |
9 pages |
| Authors:
Renee M. Marshall; TEMPLE UNIV PHILADELPHIA PA
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| Positive transcription elongation b (P-TEFb) is a general transcription elongation factor and is composed of a catalytic subunit, CDK9, and a regulatory subunit, a T-type cyclin. The complex phosphorylates the C-terminal domain of RNA polymerase II as well as negative elongation factors to allow for the transcriptional elongation of paused transcripts. We have investigated the regulation and role of cyclin T1 in breast cancer cells. While cyclin T1 expression is ... |
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*T LYMPHOCYTES
