| A Novel Strategy of Immune Modulation to Treat Lung Cancer |
Oct 2011 |
11 pages |
| Authors:
Stephen Tomlinson; CHARLESTON SOUTHERN UNIV SC
|
 | The complement system is an important effector mechanism of innate and humoral immunity. Tumor cells are protected from complement by the expression of complement inhibitory proteins on their surface, and the downregulation or blockade of these inhibitory proteins may enhance anti-tumor antibody and T cell responses. The concept that we proposed to investigate was that siRNA mediated downregulation of a complement inhibitor on lung tumor cells will sensitize the tumor ... |
|
| T-Cell Immunotherapies for Treating Breast Cancer |
Sep 2011 |
19 pages |
| Authors:
Laurence Cooper; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Breast cancer is the most commonly diagnosed cancer among U.S. women (approximately 28% or more than 1 in 4) with approximately 1 in 8 women expected to develop this malignancy over the course of her lifetime. In 2010, there are an estimated 207,000 newly diagnosed cases of invasive breast cancer resulting in about 39,800 deaths in the United States, a mortality rate higher than all other malignancies, except lung cancer. ... |
|
| TPD52: A Novel Vaccine Target for Prostate Cancer |
Sep 2011 |
20 pages |
| Authors:
Robert Bright; TEXAS TECH UNIV HEALTH SCIENCES CENTER LUBBOCK
|
| Tumor protein D52 (D52) is a novel self-onco-antigen involved in cellular transformation, proliferation and metastasis that is over-expressed in prostate cancer cells. The overall goal of this Award is to test the efficacy of D52-based vaccines in the TRAMP murine model of prostate cancer, and to characterize vaccine induced mechanisms of tumor immunity. Due to unforeseen circumstances during this funding period primarily involving the animal vendor and maternity leave for ... |
|
| Targeting Tim-1 to Circumvent Immune Tolerance in Prostate Cancer |
JUL 2011 |
10 pages |
| Authors:
Mohamed S. Arredouani; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| We have previously shown that manipulating lymphocytes through Tim1 receptor, a membrane protein that regulates the vigor and differentiation of T cells, using an agonist monoclonal antibody, enhances cytotoxic lymphocyte (CTL) responses to a model prostate tumor-associated antigen (SV40 T antigen) in tumor-free and tumor-bearing mice. This provided a tool to break immune tolerance to prostate tumor antigens in prostate cancer. We now demonstrate, using Tim1 deficient mice, that the ... |
|
| Adoptive Immunotherapy for Epithelial Ovarian Cancer Using T Cells Simultaneously Targeted to Tumor and Tumor-Associated Macrophages |
Jul 2011 |
|
| Authors:
John Maher; KINGS COLL LONDON (UNITED KINGDOM)
|
 | Adoptive T-cell immunotherapy represents an exciting advance, pioneered for hematologic malignancies and metastatic melanoma. To translate this technology to epithelial ovarian carcinoma (EOC), chimeric antigen receptors (CAR) may be used to re-target T-cell specificity against native tumor antigens. The hypothesis underlying this synergistic partnership award is that CAR-based immunotherapy of EOC will be more effective if simultaneous targeting of tumor cells and tumor-associated macrophages (TAM) is achieved. Initially, we set ... |
|
| Improve T Cell Therapy in Neuroblastoma |
Jul 2011 |
9 pages |
| Authors:
Gianpietro Dotti; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Neuroblastoma (NB) is the most common malignant extracranial tumor of childhood. Since NB appears susceptible to immunotherapies that include monoclonal antibodies and T-cell immune responses elicited by tumor vaccine, we have combined the beneficial effects of both humoral and cell-mediated components of the anti tumor response. We demonstrated indeed that adoptive transfer of Epstein-Barr-virus (EBV)-specific cytotoxic T lymphocytes (EBVCTLs) genetically modified to express a chimeric antigen receptor (CAR-GD2) targeting the ... |
|
| Enhancing the Efficacy of Prostate Cancer Immunotherapy by Manipulating T-Cell Receptor Signaling in Order to Alter Peripheral Regulatory T-Cell Activity |
Jul 2011 |
20 pages |
| Authors:
Andrew Gray; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| Immunotherapeutic strategies are a novel treatment option for incurable late-stage and metastatic prostate cancer. Several prostate-related antigens have been identified and even used clinically in therapeutic vaccine strategies, but the results have been disappointing. The activity of CD4+CD25+FOXP3+ regulatory T cells (Tregs) is a mechanism of peripheral tolerance that regulates immune responses, including those induced by therapeutic vaccination against cancer-associated antigens. PEST-domain enriched tyrosine phosphatase (PEP) is a critical negative ... |
|
| Immunotherapy of Prostate Cancer With Genetically Enhanced Tumor-Specific T-Cell Precursors |
Jun 2011 |
7 pages |
| Authors:
Marcel van den Brink; SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
|
| Precursor (Pre) T cells, when adoptively transferred further develop in the thymus into mature T cells, that is capable of lysing tumors. The overall objective of this project is to develop an effective off the shelf adoptive cell therapy with PreT cells targeting prostate cancer. To enhance the anti-tumor activity of PreT cells we transduced these cells with a chimeric antigen receptor (CAR)-Pz1 targeting the prostate cancer associated antigen - ... |
|
| Invariant NKT Cell Ligands for Prostate Cancer Vaccines |
Jun 2011 |
9 pages |
| Authors:
Steven P Balk; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Invariant natural killer T cells (iNKT cells), through their ability to mature dendritic cells (DCs) and provide help for CD4 and CD8 T cell responses, can play a major role in regulation of the cellular adaptive immune response. Our major objective in this proposal is to identify an optimal agent and method of delivery for iNKT cell activation and enhancement of cytolytic T cell responses against prostate/PCa associated antigens. Our ... |
|
| Cumulative Viral Load and Virologic Decay Patterns after Antiretroviral Therapy in HIV-Infected Subjects Influence CD4 Recovery and AIDS |
20 MAY 2011 |
11 pages |
| Authors:
Vincent C. Marconi; Greg Grandits; Jason F. Okulicz; Glenn Wortmann; Anuradha Ganesan; Nancy Crum-Cianflone; Michael Polis; Michael Landrum; Matthew J. Dolan; Sunil K. Ahuja; Brian Agan; Hemant Kulkarni; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD INFECTIOUS DISEASE CLINICAL RESEARCH PROGRAM
|
| Background: The impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown. Methods and Findings: Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope) and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U.S. Military HIV Natural History Study. CD4 and VL trajectories were computed ... |
|
| Cancer and Stroma-Targeted Immunotherapy with a Genetically Modified DC Vaccine |
01 MAY 2011 |
14 pages |
| Authors:
Xiao-Tong Song; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| While current DC vaccines are safe, their antitumor activity is limited. This is foremost due to the presence of regulatory T cells (Tregs), which create an immunosuppressive environment in breast cancer patients. In addition, there is increasing evidence that effective solid tumor vaccines have to target cancer cells as well as their supporting stroma. Thus, overcoming Treg mediated immune suppression and targeting the tumor stroma in addition to breast cancer ... |
|
| T-Cell Gene Therapy to Eradicate Disseminated Breast Cancers |
May 2011 |
103 pages |
| Authors:
Richard Junghans; ROGER WILLIAMS MEDICAL CENTER PROVIDENCE RI
|
| This Aim applies a randomization of 12 subjects to -IL2 or +IL2 arms at the maximum tolerated dose (MTD) or maximum practical dose (MPD) of designer T cells under a Phase Ib design. This will test the optimal biologic dose (OBD) in terms of the benefit of IL2 to T cell persistence and activity in vivo. There were three dose levels in the original Phase Ia: 109, 1010 and 1011 ... |
|
| T-Cell Gene Therapy to Eradicate Disseminated Breast Cancers |
May 2011 |
103 pages |
| Authors:
Richard Junghans; ROGER WILLIAMS MEDICAL CENTER PROVIDENCE RI
|
| This Aim applies a randomization of 12 subjects to IL2 or +IL2 arms at the maximum tolerated dose (MTD) or maximum practical dose (MPD) of designer T cells under a Phase Ib design. This will test the optimal biologic dose (OBD) in terms of the benefit of IL2 to T cell persistence and activity in vivo. There were three dose levels in the original Phase Ia: 109, 1010 and 1011 ... |
|
| Mechanisms of Invariant Natural Killer T Cell-Mediated Immunoregulation in Cancer |
May 2011 |
26 pages |
| Authors:
Karsten Pilones; NEW YORK UNIV NY
|
| Invariant natural killer (iNKT) cells are a unique population of immune cells that rapidly secrete a variety of cytokines upon activation and have been implicated in a autoimmune diseases, infection as well as cancer. In cancer, iNKT cells have generally been attributed potent anti-tumor functions but our studies using the murine 4T1 mammary carcinoma indicate a regulatory/ suppressive function that markedly affects response to treatment with radioimmunotherapy. We proposed to ... |
|
| Vaccination with Dendritic Cell Myeloma Fusions in Conjunction with Stem Cell Transplantation and PD-1 Blockade |
May 2011 |
10 pages |
| Authors:
David Avigan; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Most patients with multiple myeloma achieve a complete or near complete response following autologous transplantation. However, patients experience disease relapse from a persistent reservoir of chemotherapy resistant disease. There has been strong interest in developing immunotherapeutic strategies to eradicate residual disease following autologous transplantation. Our group has developed a tumor vaccine model whereby dendritic cells are fused with tumor cells. In clinical trials, vaccination with fusion cell results in anti-tumor ... |
|
| Exploiting the Immunological Effects of Standard Treatments In Prostate Cancer |
APR 2011 |
57 pages |
| Authors:
Brad H. Nelson; BRITISH COLUMBIA CANCER AGENCY VICTORIA
|
| We had previously demonstrated that hormone therapy (HT) and radiation therapy (RT) induce tumor-specific auto antibody responses in human prostate cancer, and this project investigated the clinical significance of these findings. In Aim 1, we showed that HT induces auto antibody and T cell responses against an antigen called PABPN1 in a mouse tumor model and that these immune responses are associated with inferior outcomes. We also showed that the ... |
|
| Adoptive Cellular Therapy Targeting Recurrent Pediatric Brain Cancers During Hematopoietic Recovery from High-Dose Chemotherapy |
Apr 2011 |
25 pages |
| Authors:
Duane A Mitchell; DUKE UNIV DURHAM NC SCHOOL OF MEDICINE
|
| A phase I/II clinical trial evaluating the feasibility, safety, and clinical efficacy of adoptive cellular therapy combined with dendritic cell (DC) vaccination targeting recurrent medulloblastoma and PNETs was opened for enrollment at Duke University Medical Center during the previous funding period (Year 1). DC generation and T cell expansion from archived post-induction chemotherapy specimens from five patients with medulloblastoma was attempted and mature RNA-pulsed DCs were successfully generated from 3 ... |
|
| Control of Disease Recurrence by Tumor-Infiltrating T Cells in Ovarian Cancer |
Mar 2011 |
36 pages |
| Authors:
Brad Nelson; BRITISH COLUMBIA CANCER AGENCY VANCOUVER
|
| Ovarian cancer patients with large numbers of T cells in their tumor live longer after chemotherapy compared to patients with fewer T cells in their tumor. Our goal is to use modern genomic techniques to identify the antigens recognized by these T cells, with an emphasis on new antigens that arise during chemotherapy. To this end, we are collecting matched primary and recurrent tumor tissue from ovarian cancer patients (Tasks ... |
|
| Activation and Protection of Dendritic Cells in the Prostate Cancer Environment. Addendum |
JAN 2011 |
8 pages |
| Authors:
Georgi Guruli; VIRGINIA COMMONWEALTH UNIV RICHMOND
|
| Final Report for research performed at the UMDNJ and VCU. Experiments have demonstrated for the first time the presence of endothelin receptors on murine dendritic cells (DC), and the fact of endothelin-1 production by murine DC upon stimulation with TNF dot and lipopolysaccharide (LPS). The modification of the endothelin axis on DC changed its resistance against prostate cancer induced apoptosis - the blockade of ETA receptors resulted in the increased ... |
|
| Myeloid-Derived Suppressor Cells Prevent Type 1 Diabetes in Murine Models |
Nov 2010 |
8 pages |
| Authors:
Bingjiao Yin; Ge Ma; Chun-Yu Yen; Zuping Zhou; George X Wang; Celia M Divino; Sofia Casares; Shu-Hsia Chen; Wen-Chin Yang; Ping-Ying Pan; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| Effective immunotherapy for type 1 diabetes (T1D) relies on active induction of peripheral tolerance. Myeloid-derived suppressor cells (MDSCs) play a critical role in suppressing immune responses in various pathologic settings via multiple mechanisms, including expansion of regulatory T cells (Tregs). In this study, we investigated whether MDSCs could act as APCs to induce expansion of Ag-specific Tregs, suppress T cell proliferation, and prevent autoimmune T1D development. We found that MDSC ... |
|
| Activation and Protection of Dendritic Cells in the Prostate Cancer Environment |
OCT 2010 |
23 pages |
| Authors:
Georgi Guruli; VIRGINIA COMMONWEALTH UNIV RICHMOND
|
| Final Report for research performed at the UMDNJ and VCU. Experiments have demonstrated for the first time the presence of endothelin receptors on murine dendritic cells (DC), and the fact of endothelin-1 production by murine DC upon stimulation with TNFalpha and lipopolysaccharide (LPS). The modification of the endothelin axis on DC changed its resistance against prostate cancer induced apoptosis - the blockade of ETA receptors resulted in the increased apoptotic ... |
|
| TPD52: A Novel Vaccine Target for Prostate Cancer |
SEP 2010 |
13 pages |
| Authors:
Robert K. Bright; Jennifer D. Bright; TEXAS TECH UNIV HEALTH SCIENCES CENTER LUBBOCK
|
| The overall goal of this Award is to test the efficacy of TPD52-based vaccines in the TRAMP murine model of prostate cancer, and to characterize vaccine induced mechanisms of tumor immunity. We have continued our evaluation of the ability of TPD52-DNA and/or TPD52-protein based vaccines to induce immune responses capable of rejecting the formation of subcutaneous tumors following challenge with prostate-derived TRAMP-C1 or TRAMP-C2 tumor cells. Over the past 12 ... |
|
| Enhancing Anti-Breast Cancer Immunity by Blocking Death Receptor DR5 |
SEP 2010 |
7 pages |
| Authors:
Wei-Zen Wei; WAYNE STATE UNIV DETROIT MI
|
| As described in the 2008 progress report, the revised hypothesis is that agonist DR5 Ab induced by DNA vaccination will trigger tumor cell apoptosis without compromising T cell activity. The specific aims are to (1)Construct and test DR5 vaccines to induce anti-DR5 Ab, (2) Test the agonist activity of vaccine-induced anti-DR5 Ab, and (3) Amplify anti-tumor activity of DR5 vaccination with novel chemotherapeutics. During the funding period, we established that ... |
|
| Identification and Localization of Minimal MHC-restricted CD8+ T Cell Epitopes within the Plasmodium falciparum AMA1 Protein |
24 Aug 2010 |
18 pages |
| Authors:
Martha Sedegah; Yohan Kim; Bjoern Peters; Shannon McGrath; Harini Ganeshan; Jennylynn Lejano; Esteban Abot; Glenna Banania; Maria Belmonte; Renato Sayo; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
|
| Background: Plasmodium falciparum apical membrane antigen-1 (AMA1) is a leading malaria vaccine candidate antigen that is expressed by sporozoite, liver and blood stage parasites. Since CD8+ T cell responses have been implicated in protection against pre-erythrocytic stage malaria, this study was designed to identify MHC class I-restricted epitopes within AMA1. Methods: A recombinant adenovirus serotype 5 vector expressing P. falciparum AMA1 was highly immunogenic when administered to healthy, malaria-naive adult ... |
|
| Enhanced Eradication of Lymphoma by Tumor-Specific Cytotoxic T-Cells Secreting an Engineered Tumor-Specific Immunotoxin |
JUN 2010 |
42 pages |
| Authors:
Patricia Yotnda; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| In this project, we postulate that tumor-specific T cells could be used to produce an immunotoxin (IT) targeting tumor cells only when these T cells are specifically activated by the tumor. We have engineered 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. Indeed, we have also generated a producer cell line resistant to ... |
|
| Endocrine Pancreas Regeneration |
Jun 2010 |
|
| 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. Hyperglycemia can be induced by chemical destruction of the insulin producing ... |
|
| Humanized in vivo Model for Autoimmune Diabetes |
07 MAY 2010 |
35 pages |
| Authors:
Gerald T. Nepom; BENAROYA RESEARCH INST SEATTLE WA
|
| In this study we investigated the tolerance mechanisms of high and low avidity T cells reactive to the diabetes autoantigen glutamic acid decarboxylase 65 (GAD65) and their potential role in type 1 diabetes pathogenesis. In diabetes-associated DR4 HLA humanized mice, transgenically expressing GAD65-reactive human T cells, we found that high avidity, but not low avidity, T cells can migrate to the islets and mediate a loss in pancreatic islet function. ... |
|
| PT-Cell Gene Therapy to Eradicate Disseminated Breast Cancers |
MAY 2010 |
8 pages |
| Authors:
Richard P. Junghans; ROGER WILLIAMS MEDICAL CENTER PROVIDENCE RI
|
| This represents work performed under year 1 of our Breast Cancer IMPACT award. The goals of the award are clinical trials with designer T cells in breast cancer, but also preclinical development work to bring new configurations to the clinic. Following completion of harmonization of the clinical protocol with the HSRRB, patient enrollments are expected to begin in August, 2010. Other laboratory work has been performed to begin to assess ... |
|
| Control of Disease Recurrence by Tumor-Infiltrating T Cells in Ovarian Cancer |
Mar 2010 |
97 pages |
| Authors:
Brad H Nelson; Rob Holt; John Webb; Peter Watson; BRITISH COLUMBIA CANCER AGENCY VICTORIA
|
| Ovarian cancer patients with large numbers of T cells in their tumor live longer after chemotherapy compared to patients with fewer T cells in their tumor. Our goal is to use modern genomic techniques to identify the antigens recognized by these T cells, with an emphasis on new antigens that arise during chemotherapy. To this end, we are collecting matched primary and recurrent tumor tissue from ovarian cancer patients (Tasks ... |
|
| Differential Effect of CD4+Foxp3+ T-regulatory Cells on the B and T Helper Cell Responses to Influenza Virus Vaccination |
Jan 2010 |
13 pages |
| Authors:
Jacqueline Surls; Cristina Nazarov-Stoica; Margaret Kehl; Sofia Casares; Teodor-D Brumeanu; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF MEDICINE
|
| The T-regulatory (T-reg) cells restrict the T-cell functions in various viral infections including influenza infection. However little is known about the effect of T-regs in influenza vaccination. Herein, we found that immunization of BALB/c mice with a prototype of UV-inactivated influenza PRS/A/34 virus vaccine expanded the CD4+Foxp3+ T-reg pool and fostered the development of virus-specific CD4+Foxp3+ T-reg cells. Increasing the size of Foxp3+ T-reg pool did not alter the primary ... |
|
| Vaxfectin (registered trademark) Enhances Both Antibody and In Vitro T Cell Responses to Each Component of a 5-gene Plasmodium falciparum Plasmid DNA Vaccine Mixture Administered at Low Doses |
Jan 2010 |
12 pages |
| Authors:
Martha Sedegah; William O Rogers; Maria Belmonte; Arnel Belmonte; Glenna Banania; Noelle B Patterson; Denis Rusalov; Marilyn Ferrari; Thomas L Richie; Denise L Doolan; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD MALARIA PROGRAM
|
| We previously reported the capacity of the cationic lipid-based formulation, Vaxfectin (registered trademark) to enhance the immunogenicity and protective efficacy of a low dose plasmid DNA vaccine against Plasmodium yoelii malaria in mice. Here, we have extended this finding to human Plasmodium falciparum genes, evaluating the immune enhancing effect of Vaxfectin (registered trademark) formulation on a mixture designated CSLAM of five plasmid DNA vaccines encoding antigens from the sporozoite (PfCSP, ... |
|
| 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), ... |
|
| 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 ... |
|
| 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 ... |
|
| 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 ... |
|
| 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 ... |
|
| 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. ... |
|
| 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 ... |
|
| 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 ... |
|
| 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 ... |
|
| 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 ... |
|
| 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 ... |
|
| 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 ... |
|
| 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 ... |
|
| 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 ... |
|
| 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 ... |
|
| 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 ... |
|
| 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 ... |
|
| 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 > ... |
|
| 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 ... |
|
Reports by Keyword(s)
T LYMPHOCYTES
