| Inhibition of the Protein Tyrosine Phosphatase, SHP-1, in Dendritic Cells to Enhance their Efficacy as Cell-Based Prostate Cancer Vaccines |
May-2009 |
18 pages |
| Authors:
Jonathan M Levitt; BAYLOR COLL OF MEDICINE HOUSTON TX
|
 | Early preclinical and clinical trials suggest that dendritic cell (DC)-based tumor vaccines are both feasible and safe. However, to date clinical trials of DC-based vaccines have demonstrated only limited efficacy in causing tumorregression despite eliciting measurable systemic T cell responses against prostate cancer. In an effort to enhance the effectiveness of DC-based vaccines against prostate cancer, we have tested the hypothesis that the Src homology region 2 domain-containing phosphatase-1 (SHP-1), ... |
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| CD24 as a Potential Therapeutic Target in Prostate Cancer |
Apr-2009 |
28 pages |
| Authors:
Pan Zheng; MICHIGAN UNIV ANN ARBOR
|
| This is the first annual report on the grant CD24 as a Potential Therapeutic Target in Prostate Cancer. CD24 (heat-stable antigen) is a cell surface GPI-anchored mucin-like glycoprotein with broad expression on a variety of cell types, including hematopoietic cells, neuronal cells and various epithelial cells. There are accumulating evidence showing CD24 plays an important role in tumor development and tumor metastasis. We hypothesized that the expression of CD24 on ... |
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| Innate Anti-Breast Cancer Activity of -T cells: A Novel Biological and Clinical Approach to the Treatment of Relapsed or Refractory Breast Cancer |
Mar-2009 |
13 pages |
| Authors:
Richard D Lopez; ALABAMA UNIV IN BIRMINGHAM
|
| We initially identified a specific signaling pathway which inhibits apoptosis in human -T cells. We have exploited this pathway to develop the methodologies allowing the large-scale ex vivo expansion of viable apoptosis-resistant -T cells. Importantly, we have shown that apoptosis-resistant human -T cells retain significant innate (MHC-unrestricted) cytotoxicity against a wide variety of tumor cell lines, including human breast cancer cell lines. In this project, we have focused upon testing ... |
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| Exploiting the Immunological Effects of Standard Treatments in Prostate Cancer |
Mar-2009 |
40 pages |
| Authors:
Brad H Nelson; BRITISH COLUMBIA CANCER AGENCY VANCOUVER
|
| We previously demonstrated that hormone therapy (HT) and radiation therapy (RT) induce tumor-specific autoantibody responses in human prostate cancer, and this grant investigates the clinical significance of these findings. In Aim 1, the findings that HT induces autoantibody and T cell responses against PABPN1 in the Shionogi tumor model and that these immune responses are associated with inferior outcomes have recently been submitted for publication. We have also shown that ... |
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| Combined Telomerase Inhibition and Immunotherapy in the Prevention and Treatment of Mammary Carcinomas |
01-Feb-2009 |
16 pages |
| Authors:
Jianlin Gong; BOSTON UNIV MA
|
| To determine antitumor immunity in MMT mice that are deficient for telomerase activity, we immunized MMT, G0 and G1 to G4 mTERC-/-MMT mice with DC/tumor fusion vaccine (FC/MMT). Vaccination of MMT, G0 and G1 to G4 mTERC-/-MMT mice induced CTL that lysed MUC1-positive tumor cells, suggesting that the cellular immunity is not affected by telomerase inactivity, at least in the G1 and G2 mTERC-/-MMT mice. The induction of CTL in ... |
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| CD4+ Th1 HER2-Specific T Cells as a Novel Treatment for HER2-Overexpresssing Breast Cancer |
Oct-2008 |
9 pages |
| Authors:
Vy P Lai; WASHINGTON UNIV SEATTLE OFFICE OF SPONSORED PROGRAMS
|
| During the last research year, we have made progress in two main areas. First, we have shown that neu-specific T cells can significantly inhibit growth of spontaneous mammary tumors; we plan to conduct T cell infusion studies in the spontaneous tumor model whenever possible. Second, we have made advances in understanding how and why the ex vivo cytokine environment in which the T cells are cultured impacts their clinical efficacy. ... |
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| Pulsed Electric Fields for Biological Weapons Defense |
30-Sep-2008 |
17 pages |
| Authors:
Martin A Gundersen; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES DEPT OF ELECTRICAL ENGINEERING AND ELECTROPHYSICS
|
| Pulsed power for biological investigations newly developed at USC include a fast diode-based systems designed to drive cell suspensions in a microscope slide electrode microchamber for observations of living cells during pulse exposure with pulse durations from 3 ns to 30 ns and electric fields from 1 MV/m to 10 MV/m. Nanoelectropulse responses have been observed in vitro with the following cell lines (human unless otherwise noted; ATCC catalog number ... |
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| Enhancement of Dendritic Cell-Based Immunotherapy Using a Small Molecule TGF-beta Receptor Type I Kinase Inhibitor |
01-Jun-2008 |
15 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 ... |
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| Enhanced Eradication of Lymphoma by Tumor-Specific Cytotoxic T Cells Secreting an Engineered Tumor-Specific Immunotoxin |
01-Jun-2008 |
10 pages |
| Authors:
BAYLOR COLL OF MEDICINE HOUSTON TX CELL AND GENE CENTER
|
| In this project we propose 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 needed to generate a producer ... |
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| Inhibition of the Protein Tyrosine Phosphatase, SHP-1, in Dendritic Cells to Enhance their Efficacy as Cell-Based Prostate Cancer Vaccines |
01-May-2008 |
15 pages |
| Authors:
Jonathan M Levitt; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Early preclinical and clinical trials suggest that dendritic cell (DC)-based tumor vaccines are both feasible and safe. However, to date clinical trials of DC-based vaccines have demonstrated only limited efficacy in causing tumor regression despite eliciting measurable systemic T cell responses against prostate cancer. In an effort to enhance the effectiveness of DC-based vaccines against prostate cancer, we have tested the hypothesis that the Src homology region 2 domain-containing phosphatase-1 ... |
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| Predicting the Interplay of Epitope Recognition and Evolution in RNA Viruses Under Immune Pressure |
30-Apr-2008 |
13 pages |
| Authors:
Bjoern Peters; Alesandro Sette; Martin Blythe; LA JOLLA INST FOR ALLERGY AND IMMUNOLOGY LA JOLLA CA DIVISION OF VACCINE DISCOVERY
|
| RNA viruses can rapidly mutate, causing therapeutics and vaccines to loose their effectiveness. The long-term goal of this project is to predict such mutations, in order to anticipate their effect and design better therapeutics and vaccines. In the funding period reported here, the specific goal was to build a predictive model of viral escape from immune pressure exerted by monospecific T cells in vitro. This goal was achieved: a general ... |
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| Humanized in vivo Model for Autoimmune Diabetes |
FEB 2008 |
19 pages |
| Authors:
Gerald T. Nepom; John A. Gebe; BENAROYA RESEARCH INST SEATTLE WA
|
| The CD4+ T cell response is critical for cellular autoimmunity in human T1D, but incomplete understanding of issues of specific cell frequency, avidity, function, and correlation with disease status presents major obstacles to improved therapies. This research study entails using humanized mice manifesting type 1 diabetes (T1D)-associated human HLA molecules to address the fate and pathogenicity of high and low avidity T cells reactive to the putative autoantigen glutamic acid ... |
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| Radiation Effects on the Immune Response to Prostate Cancer |
FEB 2008 |
42 pages |
| Authors:
William H. McBride; CALIFORNIA UNIV LOS ANGELES
|
| Radiation therapy (RT) is the front line treatment for prostate cancer in the early stages but is relatively ineffective against large tumor volumes and it is difficult to use it against micrometastatic disease. Immunotherapy (IT) has become popular as an alternative treatment since the discovery of prostate tumor-associated antigens (TAA) and of corresponding tumor-specific T cells in prostate cancer patients. However, IT is not a very effective modality on its ... |
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| Preclinical Evaluation of Novel Dendritic Cell-Based Prostate Cancer Vaccines |
JAN 2008 |
23 pages |
| Authors:
Natalia Lapteva; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| To enhance DC-based vaccines, we used the combination of a synthetic ligand-inducible CD40 receptor (iCD40) along with TLR-4 ligation in human monocyte-derived DCs. The iCD40 receptor permits targeted, reversible activation of CD40 in vivo, potentially bypassing the essential role of CD4+ T cells for activation of DCs. As a rigorous preclinical study of this approach, we evaluated key parameters of DC activation and function. While neither iCD40 nor TLR4 signaling ... |
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| Combining Radiotherapy and Immunotherapy to Target Surviving in Prostate Cancer |
JAN 2008 |
12 pages |
| Authors:
Dorthe Schaue; CALIFORNIA UNIV REGENTS LOS ANGELES
|
| Here, we propose to harness the immune system by immunotherapy (IT) alongside conventional radiotherapy (RT) to improve the treatment of men with advanced or recurrent prostate cancer. The overall aim is to determine whether local irradiation of prostate tumors in a preclinical and clinical setting leads to measurable tumor-specific immune responses and whether tumor vaccination can boost these immune responses possibly leading to better tumor control. Survivin is our tumor ... |
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| Interleukin-15 Increases Vaccine Efficacy through a Mechanism Linked to Dendritic Cell Maturation and Enhanced Antibody Titers |
26 NOV 2007 |
8 pages |
| Authors:
Kamal U. Saikh; Teri L. Kissner; Steven Nystrom; Gordon Ruthel; Robert G. Ulrich; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Interleukin-15 (IL-15) is generally considered to be a growth factor for natural killer cells and for sustaining T-cell memory. Previous data from our laboratory demonstrated that IL-15 is also an important factor for developing human dendritic cells. In this study, we investigated the effect of IL-15 on antibody responses to a recombinant staphylococcal enterotoxin B (SEB) vaccine (STEBVax), in a pre-clinical model of toxic-shock syndrome induced by SEB. We observed ... |
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| CD4+ Th1 HER2-Specific T Cells as a Novel Treatment for HER2-Overexpressing Breast Cancer |
OCT 2007 |
14 pages |
| Authors:
Vy P. Lai; WASHINGTON UNIV SEATTLE
|
| During the last research period, we have made significant progress in the development of our mouse neu-reactive T cell lines. First, we have confirmed the key CD4+ neu peptides (p101 and p373) most effective at priming T cell responses. Of the peptide-specific T cell lines tested, only p101- and p373- T cells induced both peptide- and protein-specific responses. In preliminary studies involving adjuvants, GMCSF was highly effective for use with ... |
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| Transfusion-Associated Microchimerism in Combat Casualties |
OCT 2007 |
8 pages |
| Authors:
James R. Dunne; Tzong-Hae Lee; Christopher Burns; Lisa J. Cardo; Kathleen Curry; Michael P. Busch; NATIONAL NAVAL MEDICAL CENTER BETHESDA MD
|
| Background: Fresh whole blood (FrWB) is routinely used in the resuscitation of combat casualties in Operation Iraqi Freedom and Operation Enduring Freedom. However, studies have shown high rates (20%-40%) of transfusion-associated microchimerism (TA-MC) in civilian trauma patients receiving allogenic red blood cell (RBC) transfusions. We explored the incidence of TA-MC in combat casualties receiving FrWB compared with patients receiving standard stored RBC transfusions. Methods: Prospective data on TA-MC at > ... |
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| Modulation of T Cell Tolerance in a Murine Model for Immunotherapy of Prostatic Adenocarcinoma. Addendum |
SEP 2007 |
11 pages |
| Authors:
Arthur A. Hurwitz; STATE UNIV OF NEW YORK UPSTATE MEDICAL CENTER SYRACUSE
|
| The goal of this project is to characterize T cell tolerance to prostate tumor antigens and to identify the role of costimulatory receptors in overcoming this tolerance. Identification of these processes will assist in the development of novel therapeutic approaches for treating prostate cancer. We use the TRAMP model a transgenic mouse line that develops primary prostatic tumors due to expression of the SV40 T antigen (TAg) under the transcriptional ... |
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| Boosting Immune Responses Against Bacterial Pathogens: In Vitro Analysis of Immunomodulators (In Vitro Analyse van de Stimulerende Werking van Verschillende Stoffen op het Immuunsysteem) |
JUL 2007 |
|
| Authors:
D. van der Kleij; TNO DEFENCE SECURITY AND SAFETY RIJSWIJK (NETHERLANDS)
|
 | The threat of the use of biological weapons, including bacteria, has increased. Bacterial resistance to antibiotics increasingly becomes a problem. Vaccination of military personnel against biothreat agents may be an option, however there is a broad range of biothreat agents, which may become even broader as a result of genetic engineering. Moreover, vaccination against multiple agents may cause undesired effects. A more generic approach to prevent the effects of a ... |
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| Targeted Lymphoma Cell Death by Novel Signal Transduction Modifications |
Jul-2007 |
25 pages |
| Authors:
Joseph M Tuscano; CALIFORNIA UNIV DAVIS DAVIS MEDICAL CENTER
|
| The proposed research set to; 1)create and characterize CD22-binding peptides that initiate signal transduction and apoptosis in NHL., 2) optimize CD22- mediated signal transduction and lymphomacidal properties of ligand blocking anti-CD22 mAbs and peptides with CD22-specific phosphatase inhibition and 3) correlate mAb-mediatedand anti-CD22 peptide-mediated in vivo physiologic changes, efficacy, and tumor targeting using advanced iPET and FDG-PET imaging technology. Since funding we have identified five peptides that are based on ... |
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| Apoptosis Use Case: In Silico Evaluation of a Library of Small Molecule Pharmacophore Models for Blocking the Formation of SEB-Major Histocompatibility Class II Complexes |
27 APR 2007 |
18 pages |
| Authors:
Rasha Hammamieh; GEORGETOWN UNIV WASHINGTON DC
|
| Staphylococcal eneterotoxin B is a superantigen produced by staphylococcus aureus. It is known to form complexes with the major histocompatibility complex class II and T-cell receptor. A recent study showed that the use of peptide antagonists failed to block the binding of SEB to MHC II and also failed to inhibit T-cell activation and cytokine production (Rajagopalan et al 2004). Since the immunopathology of SEB is T-cell dependent, inhibiting the ... |
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| Immune Suppression and Inflammation in the Progression of Breast Cancer |
MAR 2007 |
24 pages |
| Authors:
Stephanie K. Bunt; MARYLAND UNIV BALTIMORE COUNTY BALTIMORE MD
|
| Epidemiological and experimental evidence supports the concept that chronic inflammation promotes the development and progression of cancers; however, the mechanisms underlying this relationship are poorly understood. We have demonstrated previously that secretion of the pro-inflammatory cytokine interleukin 1beta (IL-1beta) from 4T1 mammary carcinoma cells (4T1/IL-1beta) promotes tumor progression and decreases the survival of tumor-bearing animals. Tumor progression in many patients and experimental animals with cancer is frequently associated with the ... |
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| Eliciting Autoimmunity to Ovarian Tumors in Mice by Genetic Disruption of T Cell Tolerance Mechanisms. Addendum |
JAN 2007 |
18 pages |
| Authors:
Brad H. Nelson; BRITISH COLUMBIA CANCER RESEARCH CENTRE VICTORIA (BRITIST COLUMBIA)
|
| We have developed a mouse model for ovarian cancer that allows monitoring of tumor-specific T cell clones as they encounter ovarian tumors in vivo. We "tagged" the neu oncogene with two defined T cell epitopes so as to confer recognition by available T cell receptor (TCR) transgenic T cells. When expressed in the murine ovarian tumor cell line ID8, epitope-tagged neu (designated neuOT1/OT2) induces the formation of aggressive ovarian adenocarcinomas ... |
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| Developing Models to Facilitate the Appropriate Selection and Effective Targeting of Candidate Antigens for Specific Cellular Immunotherapy of Prostate Cancer |
DEC 2006 |
7 pages |
| Authors:
Philip D. Greenberg; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
| Immunologically targeting prostate cancer has received increasing attention, [1- 3], in part because collateral normal tissue injury is an acceptable toxicity. However, many questions must be resolved, including the nature of antigens that can be effectively targeted, the requisite T cell response, and the relationship between tumor development and progression and the immune system. Many candidate human prostate cancer antigens have been identified, including PSA, PSMA, PAP, PSCA, and TARP ... |
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| Dendritic Cell-Based Genetic Immunotherapy for Ovarian Cancer |
DEC 2006 |
17 pages |
| Authors:
James M. Mathis; LOUISIANA STATE UNIV IN SHREVEPORT HEALTH SCIENCE CENTER
|
| 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 ... |
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| New Advanced Technology to Improve Prediction and Prevention of Type 1 Diabetes |
NOV 2006 |
39 pages |
| Authors:
Massimo Trucco; CHILDREN'S HOSPITAL OF PITTSBURGH PA
|
| Type 1 diabetes is considered an autoimmune disease characterized by the presence of inflammatory cells in the islets of Langerhans. These cells are T lymphocytes, considered responsible for the destruction of the insulin producing beta-cells present in the islets. When the majority of the beta cells are dead, the disease presents, frequently with an abrupt and clinically serious onset. The aim of this program is to determine whom among the ... |
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| Simulation of Biomolecular Nanomechanical Systems |
OCT 2006 |
34 pages |
| Authors:
Arup K. Chakraborty; Arunava Majumdar; CALIFORNIA UNIV REGENTS BERKELEY
|
| This report documents results from the BioNEMS project. Computer simulation methods and theoretical tools that can be applied to guide the design of microdevices relying on the concept of translating biomolecular binding to mechanical forces were developed. These computational tools were applied, in synergy with experiments, to define the important factors that determine device performance. One important result is that molecular-level self assembly of probe molecules determines microdevice performance, and ... |
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| Modulation of T Cell Tolerance in a Murine Model for Immunotheraphy of Prostatic Adenocarcinoma |
SEP 2006 |
28 pages |
| Authors:
Arthur A. Hurwitz; TRUE RESEARCH FOUNDATION SAN ANTONIO TX
|
| The goal of this project is to characterize T cell tolerance to prostate tumor antigens and to identify the role of costimulatory receptors in overcoming this tolerance. Identification of these processes will assist in the development of novel therapeutic approaches for treating prostate cancer. We use the TRAMP model a transgenic mouse line that develops primary prostatic tumors due to expression of the SV4O T antigen (TAg) under the transcriptional ... |
|
| Modulation of T Cell Tolerance in a Murine Model for Immunotheraphy of Prostatic Adenocarcinoma |
SEP 2006 |
28 pages |
| Authors:
Arthur A. Hurwitz; TRUE RESEARCH FOUNDATION SAN ANTONIO TX
|
| The goal of this project is to characterize T cell tolerance to prostate tumor antigens and to identify the role of costimulatory receptors in overcoming this tolerance. Identification of these processes will assist in the development of novel therapeutic approaches for treating prostate cancer. We use the TRAMP model a transgenic mouse line that develops primary prostatic tumors due to expression of the SV4O T antigen (TAg) under the transcriptional ... |
|
| Prostate Derived Ets Factor, an Immunogenic Breast Cancer Antigen |
SEP 2006 |
6 pages |
| Authors:
Ashwani Sood; HEALTH RESEARCH INC BUFFALO NY
|
| The goal of the proposed research was to test the following concept. Due to 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 Her-2/neu were compared. Two different assays were used for this purpose; the ELISPOT assay and the Cytotoxicity assay. To date, we have found ... |
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| Eliciting Autoimmunity to Ovarian Tumors in Mice by Genetic Disruption of T Cell Tolerance Mechanisms |
AUG 2006 |
15 pages |
| Authors:
Brad H. Nelson; BRITISH COLUMBIA CANCER AGENCY VANCOUVER
|
| We have developed a mouse model for ovarian cancer that allows monitoring of tumor-specific T cell clones as they encounter ovarian tumors in vivo. We "tagged" the neu oncogene with two defined T cell epitopes so as to confer recognition by available T cell receptor (TCR) transgenic T cells. When expressed in the murine ovarian rumor cell line ID8, epitope-tagged neu (designated neuOT1/OT2) induces the formation of aggressive ovarian adenocarcinomas ... |
|
| Engineered Autologous Stromal Cells for the Delivery of Kringle 5, a Potent Endothelial Cell Specific Inhibitor for Anti-Angiogenic Breast Cancer Therapy |
AUG 2006 |
27 pages |
| Authors:
Sabrina R. Perri; SIR MORTIMER B DAVIS JEWISH GENERAL HOSPITAL MONTREAL (QUEBEC)
|
| The plasminogen kringle 5 (K5) domain - which is distinct from angiostatin - possesses potent anti-angiogenic properties on its own which can be exploited in cancer therapy. We have previously shown that K5 suppresses cancer growth in tumor xenograft models, its modulation of inflammation in experimental mice with intact immune systems is unknown. To determine whether K5 possesses immune proinflammatory properties, we investigated the effects of K5 in an immune ... |
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| The Host Immune Response to Streptococcus pneumoniae: Bridging Innate and Adaptive Immunity |
06 JUL 2006 |
140 pages |
| Authors:
Katherine S. Lee; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD F EDWARD HEBERT SCHOOL OF MEDICINE
|
| Streptococcus pneumoniae (Pn) remains the primary cause of community-acquired pneumonia throughout the world, leading to high morbidity and mortality rates in the young and elderly. A better understanding of the host response to the organism would aid in the development of more effective antibiotics and vaccines. Toll-like receptors (TLRs) play an important role in the initial recognition of pathogens by binding conserved moieties known as pathogen associated molecular patterns (PAMPs). ... |
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| A Potent Oncolytic Herpes Simplex Virus for the Therapy of Advanced Prostate |
JUL 2006 |
8 pages |
| Authors:
Xiaoliu Zhang; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| ONE OF THE MAJOR LIMITATIONS FACING THE THERAPEUTIC USE OF ONCOLYTIC VIRUSES INCLUDING ONCOLYTIC HSV IS THAT THE PRE-EXISTING ANTI-VECTOR IMMUNITY CAN SUBSTANTIALLY REDUCE THE INFECTIVITY OF THE VIRUS. WE PROPOSED IN THE AIM 3 OF THIS FUNDED PROJECT TO ADDRESS THIS ISSUE WITH TWO STRATEGIES: 1) TO DELIVER ONCOLYTIC HSVS THROUGH LIPOSOME-FORMULATED VIRAL DNA INSTEAD OF THE TRADITIONAL VIRAL PARTICLES AND 2) TO USE T-LYMPHOCYTES AS A CARRIER FOR ... |
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| Lowering T Cell Activation Thresholds and Deregulating Homeostasis to Facilitate Immunotherapeutic Responses to Treat Prostate Cancer |
01 JUN 2006 |
7 pages |
| Authors:
Eugene D. Kwon; MAYO CLINIC ROCHESTER MN
|
| The inductor of tumor-specific T cells remains a primary obstacle to immunotherapeutic approaches for most cancers including prostate cancer This difficulty has been largely ascribed to mechanisms for tumor evasion of the immune system and host-imposed restrictions (collectively referred to as tolerance) that prevent cross-reactive autoimmunity against the parent tissues from which tumors arise. Limitations in techniques to identify novel and truly immunogenic prostate-spew antigens and efficient methods to modify ... |
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| Naked DNA Immunization of Prevention of Prostate Cancer in a Dunning Rat Prostate Tumor Model |
JUN 2006 |
93 pages |
| Authors:
Milcho Mincheff; GEORGE WASHINGTON UNIV WASHINGTON DC
|
| After cloning a truncated (no peptide leader sequence) versions of the human prostate acid phosphatase (H-PAP-T), the human prostate-specific antigen (HPSA- T) and the rat analogue of the human PSMA (R- PSMA -S), all plasmids were produced under GLP conditions. Their safety was tested in rats and the efficacy to stimulate T cells and to prevent development of transplantable tumors was shown in a rat model. Best protection was obtained ... |
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| Phase II Study of HER-2/neu Intracellular Domain Peptide-Based Vaccine Administered to Stage IV HER2 Positive Breast Cancer Patients Receiving Trastuzumab |
MAY 2006 |
9 pages |
| Authors:
Mary L. Disis; SEATTLE UNIV WA
|
| The primary purpose of this grant is to determine the overall survival benefit in Stage IV HER2 positive breast cancer patients vaccinated with a HER2 ICD peptide-based vaccine while receiving maintenance trastuzumab. The scope of the work includes a Phase II single arm study of a HER2 ICD peptide based vaccine given concurrently with trastuzumab. Patients enrolled will be HER2 over expressing stage IV breast cancer patients who have been ... |
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| Evaluation of Listeria Monocytogenes Based Vaccines for HER-2/neu in Mouse Transgenic Models of Breast Cancer |
MAR 2006 |
25 pages |
| Authors:
Reshma Singh; PENNSYLVANIA UNIV PHILADELPHIA
|
| HER-2/neu is a 185 kDa transmembrane protein that is a member of the epidermal growth factor family of receptors and is over expressed on 25-40% of all breast cancers. Five Listeria monocytogenes vaccines have been made consisting of fragments of HER-2/neu that are capable of stopping the growth of transplantable tumors in wild type FVB/N mice and can cause the eventual regression of about 30% of these tumors. Four of ... |
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| Intra-Prostate Cancer Vaccine Inducer |
FEB 2006 |
56 pages |
| Authors:
Robert E. Humphreys; ANTIGEN EXPRESS INC WORCESTER MA
|
| A large amount of effort has been focused on the optimization of human Ii-RNAi constructs during the past year. We have optimized the use of a combination of human Ii-RNAi constructs, which target different sites of Ii mRNA, to obtain optimal Ii suppression. More importantly, we have defined the influence of the promoter on the activity of Ii-RNAi. Our results indicate that two elements are important for the activity of ... |
|
| CTLA-4 Blockade-Based Immunotherapy in Prostate Cancer |
JAN 2006 |
9 pages |
| Authors:
Brian I. Rini; CALIFORNIA UNIV SAN FRANCISCO
|
| CTLA-4 is an inhibitory molecule on T cells that induces T cell downregulation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth and survival factor for dendritic cells. The safety of combining GM-CSF with CTLA-4blockade in prostate cancer patients is being investigated in an ongoing phase I trial. Methods: Sequential cohorts of 3-6 patients receive GM-CSF 250mug/m2/d subcutaneously on days 1-14 of a 28-day cycle withescalating doses of anti-CTLA antibody on day ... |
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| De Novo Synthesis of Marburg Virus Antigens from Adenovirus Vectors Induce Potent Humoral and Cellular Immune Responses |
09 DEC 2005 |
13 pages |
| Authors:
Danher Wang; Alan L. Schmaljohn; Nicholas U. Raja; Charles M. Trubey; Laure Y. Juompan; Min Luo; Stephen B. Deitz; Hong Yu; Jan Woraratanadharm; David H. Holman; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Marburg virus (MARV) is an African filovirus that causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, there are no MARV vaccines or therapies approved for human use. We hypothesized that developing a vaccine that induces a de novo synthesis of MARV antigens in vivo will lead to strong induction of both a humoral and cell-mediated immune response against MARV. Here, we develop and characterize three ... |
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| Phase I Trial of Adenovirus-Mediated IL-12 Gene Transduction in Patients with Recurrent Locally Advanced Prostate Cancer Following Therapy |
01 OCT 2005 |
29 pages |
| Authors:
Simon J. Hall; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| Patients with radiorecurrent prostate cancer have few options. Gene therapy may define a treatment option of both local and systemic value. Pre-clinical studies using adenovirus-mediated (Ad.) transduction of IL-12 (Ad.mIL-12) in a metastatic model of prostate cancer resulted in local growth suppression, survival enhancement and inhibition of pre-established metastases. The basis for these activities include the induction of both innate (neutrophils & NKs) and acquired immunity (T cells). On the ... |
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| Secondary Lymphoid Tissue Chemokine as an Immunotherapeutic Against Primary and Metastatic Breast Cancer |
28 SEP 2005 |
8 pages |
| Authors:
Heth R. Turnquist; NEBRASKA UNIV AT OMAHA
|
| To generate anti-tumor immune responses, T cells must interact with mature dendritic cells (DCs) presenting tumor-derived peptides. Natural killer (NK) cells, DCs, and T cells express a common receptor, CCR7, which binds the chemokine SLC/CCL21. SLC/CCL21 is normally expressed in the lymphoid organs and coordinates the interactions between DCs and T cells, thus initiating T cell responses. In Task 1, we examined the effect of SLC/CCL21 administered via a sustained ... |
|
| Enhancing Anti-Prostate Cancer Immunity through OX40 Engagement |
28 SEP 2005 |
8 pages |
| Authors:
Andrew D. Weinberg; PROVIDENCE PORTLAND MEDICAL CENTER OR
|
| 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 of ... |
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| Chemotherapeutics Targeting Immune Activation by Staphylococcal Superantigens |
01 SEP 2005 |
|
| Authors:
Teresa Krakauer; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Staphylococcal enterotoxin B (SEB) and related superantigenic toxins are potent activators of the immune system and cause a variety of diseases in humans, ranging from food poisoning to toxic shock. These toxins bind to both MHC class II molecules and specific V-beta regions of T cell receptors (TCR), resulting in the activation of both monocytes/macrophages and T lymphocytes. The interactions of these toxins with host cells lead to excessive production ... |
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| Universal Breast Cancer Antigens as Targets Linking Early Detection and Therapeutic Vaccination |
SEP 2005 |
73 pages |
| Authors:
Susan M. Domchek; PENNSYLVANIA UNIV PHILADELPHIA
|
| This grant supports studies to understand the potential of universal tumor antigens for cancer immunotherapy, with a particular focus on the characterization of the human telomerase reverse transcriptase (hTERT) as tumor antigen. Telomerase is expressed by >90% of all human breast cancers but absent in most normal cells. Telomerase function has been directly linked to oncogenesis and its inhibition in telomerase-positive human tumors leads to growth arrest. Following a series ... |
|
| Birth Weight and Acute Childhood Leukemia: A Meta-analysis of Observational Studies |
17 AUG 2005 |
130 pages |
| Authors:
Jean Taylor; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF PREVENTIVE MEDICINE AND BIOMETRICS
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| The major objective of this study was to determine whether high birth weight is associated with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) among children, and to quantify the strength of the relationships. The author conducted a meta-analysis of nine case-control studies (published between 1991 and 2004) encompassing over 6,200 children with ALL and over 12,000 controls. She found that children weighing 4,000 grams or more at birth ... |
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| Eliciting Autoimmunity to Ovarian Tumors in Mice by Genetic Disruption of T Cell Tolerance Mechanisms |
AUG 2005 |
13 pages |
| Authors:
Brad H. Nelson; BRITISH COLUMBIA CANCER RESEARCH CENTRE VICTORIA (BRITIST COLUMBIA)
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| Research in the fields of basic immunology and autoimmunity has identified several distinct mechanisms through which immune tolerance is established and maintained in the normal host, and additional mechanisms will likely be identified in future. We hypothesize that ovarian tumors are recognized in an antigen-specific manner by T cells but induce immunologic tolerance through one or more of these homeostatic mechanisms, which have evolved to protect the host from autoimmune ... |
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| Mechanisms of Graft-vs.-Leukemia Against a Novel Murine Model of Chronic Myelogenous Leukemia |
JUL 2005 |
8 pages |
| Authors:
Warren D. Shlomchik; YALE UNIV NEW HAVEN CT
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| Our objective is to understand the immunobiology underlying the differential sensitivity of chronic phase and blast crisis CML. Our data thus far support the hypothesis that GVL against mCP-CML can be mediated by redundant processes, and that impairment of an individual pathway is insufficient to prevent GVL. We hypothesize that GVL against BC-CML is less forgiving than that against CP-CML, and that multiple effector pathways must act in concert for ... |
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Reports by Keyword(s)
T LYMPHOCYTES
