| The Use of Venezuelan Equine Encephalitis Replicons Encoding the Her-2/ neu Tumor Associated Antigen for the Prevention and Treatment of Breast Cancer |
MAY 2002 |
7 pages |
| Authors:
Brian R. Long; Roland M. Tisch; NORTH CAROLINA UNIV AT CHAPEL HILL
|
 | Overexpression and amplification of the Her-2/neu proto-oncogene has been implicated in the development of aggressive human breast cancer. Consequently, Her-2/neu provides a potential target for immunotherapy. Indeed, Her-2/neu specific cytotoxic T lymphocytes (CTL) can be detected in patients with breast and ovarian cancer. Nevertheless, the observed response to Her-2/neu is inadequate to prevent tumor progression. Our overall goal is to determine whether genetic vaccination is a feasible strategy to enhance ... |
|
| Tumor Associated Antigenic Peptides in Prostate Cancer |
MAR 2002 |
77 pages |
| Authors:
Raj K. Tiwari; NEW YORK MEDICAL COLL VALHALLA
|
| We had earlier demonstrated the prophylactic and therapeutic efficacy of tumor derived heat shock protein, gp96-peptide complexes. Since this tumor rejection property was specifically mediated by tumor derived and not non-tumor derived gp96-peptide complexes, and that gp96 preparations stripped of its peptides are non-immunogenic, we examined the hypothesis whether prostate cancer associated peptides which may act as tumor rejection antigens can be identified in gp96-peptide complexes utilizing a combinatorial single ... |
|
| Development of a Novel Methodology for Improving CTL Recognition of Prostate Specific Antigen (PSA) for the Immunotherapy of Prostate Cancer |
MAR 2002 |
24 pages |
| Authors:
John G. Frelinger; ROCHESTER UNIV NY
|
| The major goal of the proposed research is to develop a novel methodology for improving T cell epitopes. The underlying hypothesis is that T cells capable of recognizing tumor- associated antigens (TAA) are present but often difficult to activate. However, once activated such T cells might be effective against tumors due to the less stringent triggering requirements of mature effectors. We proposed to develop a novel bacterial expression system for ... |
|
| The Role of Th1/Th2 Cytokine Balance in Gulf War-Related Illness |
FEB 2002 |
47 pages |
| Authors:
Mark Peakman; KING'S COLL LONDON (UNITED KINGDOM)
|
| The aetiology of Gulf-War (GW) related illnesses remains unclear. The proposal has made that multiple vaccines, given under the stress of deployment with additional effects of the T helped 2 (Th2) adjuvant pertuseia could skew the immune response towards a Th2 profile. The Th2 profile, characterized by the cytokines interleukin-4 (IL-4) and IL-10, has been associated with symptoms such as allergic disease, hypersensitivity and depression, symptoms characteristic of which are ... |
|
| Androgen Ablation Combined with CTLA-4 Blockage-Based Immunotherapy as a Treatment for Prostate Cancer |
JAN 2002 |
13 pages |
| Authors:
Eugene D. Kwon; LOYOLA UNIV MAYWOOD IL
|
| Manipulations capable of repealing host tolerance to induce T cell- mediated prostate tissue specific responses are of central importance to immunotherapeutic approaches to prostate cancer treatment. Hence in the current proposal, we test whether androgen ablation (by castration) can induce T cell responses targeting murine prostate epithelial and tumor cells. We previously showed that castration of TRAMP mice results in prostate and tumor infiltration by antigen presenting cells (APC's) as ... |
|
| Prostate Tumor Antigen Discovery: Development of a Novel Genetic Approach |
DEC 2001 |
|
| Authors:
Dean L. Mann; MARYLAND UNIV BALTIMORE
|
 | The overall objective of this study was to determine the in vitro immunogenicity of products of prostate tumors that could potentially be used as tumor vaccines. To achieve this goal, the following specific tasks were undertaken: (1) detection of recall T cell responses to known tumor antigens, (2) optimization of antigen delivery to and presentation by dendritic cells (DC), and (3) develop oligonucleotide-derived tumor antigens in cDNA libraries. T cell ... |
|
| New Advanced Technology to Improve Prediction and Prevention of Type I Diabetes |
NOV 2001 |
27 pages |
| Authors:
Massimo Trucco; CHILDREN'S HOSPITAL OF PITTSBURGH PA
|
| Type 1 diabetes is considered an autoimmune disease characterized by the presence of lymphocytes in the islets of Langerhans. The majority of infiltrating cells are actually T lymphocytes that are considered responsible for the destruction of the insulin producing beta-cells present in the islets. When the number of dead cells reach 85-90% of the originally existing beta- cells, the disease presents, frequently with an abrupt and clinically serious onset. Individuals ... |
|
| Epstein-Barr Virus: A Role for a Tumorigenic Virus in the Etiology of Breast Cancer |
OCT 2001 |
17 pages |
| Authors:
Richard M. Longnecker; NORTHWESTERN UNIV EVANSTON IL
|
| This proposal aimed to examine the role of a tumorigenic virus, Epstein-Barr virus (EBV), in etiology of breast cancer. EBV is an almost ubiquitous human herpesvirus that establishes lifetime latent infections in humans. It was the first human tumor virus discovered through its association with Burkitt's lymphoma in Africa. EBV infection also associates with various malignancies and proliferative syndromes, mainly affecting lymphoid and epithelial tissues. In lymphoid tissues these include ... |
|
| P53 Immune Response in Breast Cancer Patients: Assessment of CTL recognizing the HLA-A2.1 Restricted, Wild-Type Sequence p53 264-272 Epitope |
OCT 2001 |
26 pages |
| Authors:
Albert B. DeLeo; PITTSBURGH UNIV PA
|
| Approximately 30% of breast cancer patients are p53 sero-positive and have detectable anti-p53 T cell proliferative responses. Tumors expressing mutant p53 molecules have an enhanced potential to present wild- type-sequence (wt) p53 epitopes derived from mutant p53 for T-cell recognition. Vaccines targeting these epitopes would be broadly applicable. HLA-A2.l-restricted CTL- recognizing wt P53 264-272 and 149-157 peptides have been generated from PBMC obtained from healthy donors and/or oral cancer patients. ... |
|
| Involvement of the Tyrosine Phosphatase SHP-1 in the Development of Breast Cancer |
OCT 2001 |
43 pages |
| Authors:
Ulrike M. Lorenz; VIRGINIA UNIV CHARLOTTESVILLE
|
| Purpose: To test the working hypothesis that SHP-1 is essential for controlling growth and differentiation of mammary epithelial cells and that its dysregulation contributes to the development of breast cancer. Scope: To biochemically and functionally characterize SHP-1 in human breast cancer cell lines and to define its biological function in normal epithelial cells. Major Findings: We have shown that SHP-1 localizes to the lipid raft. Moreover, our data indicate a ... |
|
| Enhancing Malaria Vaccine Development by the Naval Medical Research Center |
26 SEP 2001 |
18 pages |
| Authors:
David D. Hile; Debra J. Trantolo; CAMBRIDGE SCIENTIFIC INC CAMBRIDGE MA
|
| A priority of DoD is to develop effective vaccines for preventing malaria. Developing malaria vaccines is complicated by the complexity of the parasite and of the human host's response to the infection. Developing sustainably effective vaccines requires a vaccine delivery system that can accommodate a complex variety of biologicals targeted for immune stimulation. In this project, DNA plasmid-based vaccines were encapsulated within biodegradable polymer microparticles using proprietary techniques. The delivery ... |
|
| Strategic Manipulation of Tumor Antigens to Enhance Immunogenicity |
SEP 2001 |
26 pages |
| Authors:
Allan D. Hess; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOLOF MEDICINE
|
| Systemic chemotherapy including high dose chemotherapy with stem cell rescue frequently induces responses in women with metastatic breast cancer Unfortunately, disease often recurs due to the persistence of chemotherapy resistant tumor cells. The immune system can effectively target and kill chemotherapy resistant tumor cells. Tumor associated antigens particularly antigens derived from the Her-2/neu oncogene can be recognized in breast cancer. Strategies to enhance immune recognition of these antigens may provide ... |
|
| Immunogenicity of Well-Characterized Synthetic Plasmodium Falciparum Multiple Antigen Peptide Conjugates |
AUG 2001 |
8 pages |
| Authors:
Manju B. Joshi; Albert A. Gam; Robert A. Boykins; Sanjai Kumar; John Sacci; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
|
| Given the emerging difficulties with malaria drug resistance and vector control, as well as the persistent lack of an effective vaccine, new malaria vaccine development strategies are needed. We used a novel methodology to synthesize and fully characterize multiple antigen peptide (MAP) conjugates containing protective epitopes from P!asmodium falciparum and evaluated their immunogenicity in four different strains of mice. A di-epitope MAP (T3-T1) containing two T-cell epitopes of liver stage ... |
|
| Antitumor Activity Correlates with the Generation of Breast Tumor Specific Type 1 T Cells |
AUG 2001 |
25 pages |
| Authors:
Bernard A. Fox; PROVIDENCE PORTLAND MEDICAL CENTER OR
|
| When vaccination fails to protect the host from a subsequent challenge with a tumor, that tumor is generally characterized as nonimmunogenic. This designation suggests that the host has not recognized, or is tolerant of the tumor antigens. Our recent studies suggest that this is not true. We have demonstrated that progressively growing subcutaneous tumors sensitize tumor-specific T cells; however, the antigen-reactive T cells are polarized to secrete type 2 (T2) ... |
|
| Immunological Prevention of Spontaneous Mammary Carcinoma in Transgenic Mice |
AUG 2001 |
139 pages |
| Authors:
Guido Forni; TURIN UNIV (ITALY)
|
| Our program was to evaluate the ability of non specific and specific immunity to hamper the carcinogenesis. The ultimate goal was to determine whether this type of approach can be rationally applied in humans at risk. The model used consisted in virgin female mice transgenic for the activated (BALB- neuT) or amplified (FVB-neuN) rat Her-2/neu oncogene. BALB-neuT mice progress rapidly to multiple mammary carcinomas, while in FVB-neuN carcinogenesis is slow. ... |
|
| A Molecular Approach for Development of Vaccines Against Cardiotropic and Pancreatropic Strains of Coxsackievirus B |
JUL 2001 |
135 pages |
| Authors:
Massimo Trucco; CHILDREN'S HOSPITAL OF PITTSBURGH PA
|
| High frequencies of T-cell receptor (TCR) VBeta7+ T-cells are detected among lymphocytes isolated from pancreatic islets of children at the onset of Type 1 diabetes. Peripheral blood mononuclear cells from recently- diagnosed diabetic patients and from patients with diabetes from 2 to 14 years of duration were analyzed to assess whether a preferential expression could also be detected among them. TCR VBeta7 gene expression in patients who converted to diabetes ... |
|
| Regulation of Tumor Progression by Mgat5-Dependent Glycosylation |
JUL 2001 |
43 pages |
| Authors:
James W. Dennis; MOUNT SINAI HOSPITAL TORONTO (ONTARIO)SAMUEL LUNENFIELD RESEARCH INST
|
| Task 1 was to further define the phenotype of Mgat5(-/-) cells regarding adhesion, signal transduction, and growth factor responsiveness. We have established immortalized embryonic fibroblast cell lines form Mgat5(-/-) mice, made Mgat5 retrovial vector for rescue of the mutant phenotypes, and established new technology (the Cellomics scan array system) to measure these parameters with precision. Task 2 was to use genetic methods to analysis Mgat5 dependent tumor progression in vivo. ... |
|
| Enhanced T Cell Attack of Brain Micro-Metastases |
JUL 2001 |
14 pages |
| Authors:
Lois Lampson; BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
|
| Our goal is to increase the efficacy of T cell attack against breast cancer that has metastasized to the brain. This is a major clinical problem, and T cell therapy is well-suited to attack of tumor that may be difficult to image or access conventionally. The first task was to develop a suitable model: (1) We adapted methods for introducing tumor into the carotid artery, to favor delivery to the ... |
|
| Effect of Tumor Derived TGF-Beta on the Efficacy of Dendritic Cell Vaccines |
JUL 2001 |
10 pages |
| Authors:
James J. Kobie; Emmanuel T. Akporiaye; ARIZONA UNIV TUCSON
|
| As antigen presenting cells capable of inducing strong cytotoxic T lymphocyte (CTL) responses to specific antigens, dendritic cells (DCs) have become prime candidates for use in cancer immunotherapy. it has been shown that treatment of DCs with tumor cell supernatants results in reduced expression of MHC class II and reduced ability to induce a CTL. response. These findings have led to the suggestion that tumors secrete soluble factors that inhibit ... |
|
| Designer T Cells for Breast Cancer Therapy: Phase I Studies |
JUL 2001 |
85 pages |
| Authors:
Richard P. Junghans; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| In the present report we describe studies using chimeric immune receptors consisting of an antibody fragment against the CEA tumor antigen joined to signaling portions of the T cell receptor(IgTCR) . The antibody fragment confers CEA specificity to the receptor, while the signaling domains transmit T cell activation signals. These receptors allow the T cells (designer T cells) to bypass immune tolerance to CEA and to activate effector functions in ... |
|
| The Role of Breast Cancer Derived Prostaglandin E2 in the Elaboration of a Therapeutic Immune Response |
JUL 2001 |
19 pages |
| Authors:
Stephen L. Eck; PENNSYLVANIA UNIV PHILADELPHIA
|
| The principal goal was to understand why breast cancer cells are able to evade the host immune system despite the presence of tumor antigens and tumor antigen-specific T lymphocytes. We had previously demonstrated that tumor- derived prostaglandin E2 (PGE2) directly contributes to the lack of a significant immune response to breast cancer cells. However, the production of PGE2 by breast cancer cells did not completely explain the immune suppressive effect ... |
|
| Novel Vectors for Dendritic Cell Transduction |
JUN 2001 |
7 pages |
| Authors:
Theresa V. Strong; ALABAMA UNIV IN BIRMINGHAM
|
| Dendritic cells (DCs) show promise for cancer immunotherapy due to their critical role in mediating immune response. Development of an optimal DC transduction protocol for tumor antigen presentation would represent a significant advancement in DC-based vaccination strategies. We are evaluating novel vector systems for dendritic cell transduction. Replicative RNA transcripts based on the alphavirus family are noninfectious vectors capable of directing cytoplasmic replication and high level transgene expression upon entry ... |
|
| Dissecting the Immunogenicity of Monoclonal Antibodies |
JUN 2001 |
11 pages |
| Authors:
Christopher M. Snyder; Lawrence J. Wysocki; NATIONAL JEWISH MEDICAL AND RESEARCH CENTER DENVER CO
|
| The potential of mononclonal antibodies, (mAbs), for use in therapeutic and diagnostic applications has not been fully realized in part due to counter-immune responses that often arise in patient recipients of mAb. A growing research effort to humanize mAb has focused primarily on the structure or sequence of the antibody variable (V) region domains. However, these approaches may ultimately suffer, as they overlook the requirement of T cell help for ... |
|
| The Use of Exercise to Increase CD4 (+) T Lymphocytes Following Chemotheraphy Treatment for Breast Cancer |
JUN 2001 |
21 pages |
| Authors:
Andrea M. Mastro; PENNSYLVANIA STATE UNIV UNIVERSITY PARK
|
| T helper, CD4+ lymphocytes, recover slowly following chemotherapy. in healthy females. Exercise increased CD4+ cells. Our goal was to determine if exercise helped CD4+ cells recover following chemotherapy. Blood lymphocytes, before and after chemotherapy/radiation and 3 and 6 months of exercise were assayed for proliferation and for expression of leukocyte antigens. Following fitness testing, the subjects exercised with a trainer. |
|
| Characterization of the Structure and Immunogenicity of HN654-662 and Variant Peptides Bound to HLA-A2.1 |
APR 2001 |
75 pages |
| Authors:
Ashwami K. Sharma; Edward Collins; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| We propose to establish an approach by which tumor cells are eradicated through selective induction of CD8(+) cells specific for a cellular protein, HER-2/neu, that is expressed in many breast and ovarian cancers. Our model system is the class I MHC molecule HLA-A2.1 and the HER-2/neu protein. HLA-A2.1 is present in approximately 50% of Caucasian and African-American women, and HER-2/neu is over-expressed in approximately 30% of breast tumors. A peptide ... |
|
| Development of a Novel Methodology for Improving CTL Recognition of Prostate Specific Antigen (PSA) for the Immunotherapy of Prostate Cancer |
MAR 2001 |
12 pages |
| Authors:
John Frelinger; ROCHESTER UNIV NY
|
| The major goal of the proposed research is to develop a novel methodology for improving T cell epitopes. The underlying hypothesis is that T cells capable of recognizing tumor-associated antigens (TAA) are present but often difficult to activate. However, once activated such T cells might be effective against tumors due to the less stringent triggering requirements of mature effectors. We proposed to develop a novel bacterial expression system for modifying ... |
|
| Tumor Associated Antigenic Peptides in Prostate Cancer |
MAR 2001 |
38 pages |
| Authors:
Raj Tiwari; NEW YORK MEDICAL COLL VALHALLA
|
| We had earlier demonstrated the prophylactic and therapeutic efficacy of tumor derived heat shock protein, gp96-peptide complexes. Since this tumor rejection property was specifically mediated by tumor denved and not non-tumor derived gp96-peptide complexes, and that gp96 preparations stripped of its peptides are non-immunogenic, we examined the hypothesis whether prostate cancer associated peptides which may act as tumor rejection antigens can be identified in gp96-peptide complexes utilizing a combinatorial single ... |
|
| Androgen Ablation Combined With CTLA-4 Blockade-Based Immunotherapy as a Treatment for Prostate Cancer |
JAN 2001 |
9 pages |
| Authors:
Eugene D. Kwon; LOYOLA UNIV OF CHICAGO IL
|
| Manipulations capable of repealing host tolerance to induce T cell- mediated prostate tissue-specific responses are of central importance to immunotherapeutic approaches to prostate cancer treatment. Hence in the current proposal, we test whether androgen ablation (by castration) can induce T cell responses targeting murine prostate epithelial and tumor cells. To date, we have found that castration of TRAMP mice results in prostate and tumor infiltration by antigen presenting cells (APC's) ... |
|
| The Quantitative Immunophenotype (QuIP) is Characteristic of Individuals |
14 DEC 2000 |
29 pages |
| Authors:
Doug Redelman; Wayne Ensign; Donald E. Roberts; NAVAL HEALTH RESEARCH CENTER SAN DIEGO CA
|
| The clusters of differentiation (CD) molecules used to identify lineages of cells often have important functional activities. Furthermore, the numbers of CD molecules expressed per cell can reflect the status of cell lineages. For example, B cells with abnormal numbers of CD19 per cell have altered capacities to produce antibody responses. Therefore, the quantitative immunophenotype (QuIP), i.e., both the numbers of cells in various populations and the numbers of CD ... |
|
| Immunity to HER-1/neu Protein |
OCT 2000 |
17 pages |
| Authors:
Mary L. Disis; UNIV OF WASHINGTON SEATTLE
|
| The HER-2/neu (HER2) proto-oncogene is amplified and overexpressed in 20-40% of invasive breast cancers. HER2 over-expression is associated with aggressive disease and is an independent predictor of poor prognosis in several subsets of patients. The overall goal for the proposal is to develop the knowledge base necessary to develop vaccine and T cell therapy strategies directed against HER2. Preliminary studies prior to the grant discovered that some patients with breast ... |
|
| Randomized Trial of Interleukin-2 (IL-2) as Early Consolidation Following Marrow Ablative Therapy with Stem Cell Rescue for Metastatic Breast Cancer |
OCT 2000 |
11 pages |
| Authors:
Wolfram E. Samlowski; UTAH UNIV SALT LAKE CITY
|
| Marrow ablative doses of chemotherapy followed by stem cell rescue (MAT/SR) produce a high frequency of objective responses in patients with metastatic breast cancer, with up to 40-50 % complete responses. Unfortunately, responses tend to be short-lived. Interleukin-2 (IL-2) can activate lymphocytes to kill multidrug resistant cancer cells. Our phase I data established that a single course of low-dose IL-2 (1.6 million IU/m2/day as a continuous i.v. infusion for 18 ... |
|
| Characterization of CTL Recognized Epitopes on Human Breast Tumors |
OCT 2000 |
89 pages |
| Authors:
Constantin G. Ioannides; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Studies supported by this grant lead to identification of three novel antigens presented by breast cancer cells, which are recognized by cytotoxic T lymphocytes (CTL). These tumor antigens are: (1) HER-2 (HER-2/neu proto- oncologene product), (2) folate binding protein (FBP), folate receptor - alpha, and (3) amino enhancer of split (AES), a transcription factor associated with the Notch complex. These epitopes associated with these antigens were identified in association with ... |
|
| A Novel Gene Gun-Mediated IL-12 Gene Therapy for Breast Cancer |
OCT 2000 |
37 pages |
| Authors:
Ning-Sun Yang; POWDERJECT VACCINES INC MADISON WI
|
| The results of this study show that particle-mediated IL-12 gene therapy was effective against mammary tumors in mouse models. IL-12 gene therapy of the immunogenic TS/A adenocarcinoma resulted in regression of the established primary tumors and induction of immunological memory. This IL-12 gene therapy protocol for the poorly immunogenic 4T1 adenocarcinoma did not significantly affect the growth of the primary tumor, but could reduce spontaneous metastasis into the lungs. The ... |
|
| Stimulating CTL Towards HER2/neu Overexpressing Breast Cancer |
OCT 2000 |
|
| Authors:
Edward J. Collins; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| We proposed to establish an approach by which tumor cells are eradicated through selective induction of CD8+ T cells specific for a protein overexpressed in many adenocarcinomas. A peptide derived from HER-2/neu (HN654-662, GP2) stimulates cytotoxic T lymphocytes (CTL) that lyse primary tumors from ovarian or breast cancers. It has been proposed that the poor immunogenicity of GP2 is due to poor binding to HLA-A2.l. Our data demonstrate GP2 is ... |
|
| Deprenyl and Protection Against Mammary Tumors |
SEP 2000 |
|
| Authors:
David L. Felten; LOMA LINDA UNIV CA
|
| L-deprenyl, a monoamine oxidase-B inhibitor, has been reported to reverse the age-related decline in sympathetic noradrenergic innervation and immune function in old rats and enhance cell-mediated immunity in tumor-bearing rats. The aim of the present set of studies was to investigate whether deprenyl treatment of young and old female rats with carcinogen-induced and spontaneously developing mammary tumors, and middle-aged female rats could inhibit tumor development and growth. Also, the effects ... |
|
| New Strategy for the Redirection of Cytolytic T Lymphocytes to Breast Tumors |
SEP 2000 |
60 pages |
| Authors:
Zelig Eshhar; WEIZMANN INST OF SCIENCE REHOVOT (ISRAEL)
|
| The main objective of this research project has been to apply the T- body approach for the immunotherapy of breast cancer. To this end we have altered the specificity of patient-derived lymphocytes through stable modification with chimeric receptor genes consisting of either an anti-breast tumor single-chain variable (scFv) region of anti- HER2 antibody or the Erb-B NDF ligand linked to a T cell activation molecule (the gamma subunit of the ... |
|
| Epitope Specific T Cell Immunity to Breast Cancer |
AUG 2000 |
91 pages |
| Authors:
Constantin Ioannides; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Studies during the ongoing grant period demonstrated that: (1) the CTL epitope E75 is partial agonist for activation of CTL effector function. It frequently activates IFN-gamma secretion, but infrequently cytolysis. (2) Enhancement of E75 immunogenicity can be achieved by methylene (CH2)-extension at positions in the peptide determined by computer assisted modeling to point upwards and sideways (Alanine position 7). In addition enhanced survival and maintenance of cytolytic activity by E75 ... |
|
| Antitumor Activity Correlates With the Generation of Breast Tumor Specific Type 1 T Cells |
AUG 2000 |
|
| Authors:
Bernard Fox; PROVIDENCE PORTLAND MEDICAL CENTER OR
|
| When vaccination fails to protect the host from a subsequent challenge with a tumor, that tumor is generally characterized as nonimmunogenic. This designation suggests that the host has not recognized, or is tolerant of the tumor antigens. Our recent studies suggest that this is not true. We have demonstrated that progressively growing subcutaneous tumors sensitize tumor-specific T cells; however, the antigen-reactive T cells are polarized to secrete type 2 (T2) ... |
|
| The Advantages of Multi-Epitope Tumor Antigens as an Approach to Treating Breast Cancer |
JUL 2000 |
11 pages |
| Authors:
Sylvia Kiertscher; CALIFORNIA UNIV LOS ANGELES
|
| Dendritic cells (DC) are an integral part of the immune system's response to cancer. A number of clinical trials have been initiated to use these cells in the treatment of melanoma, prostate cancer, and lymphoma. In preparation for treating breast cancer patients with DC, this proposal examines a fundamental issue that needs to be resolved before proceeding with this exciting new therapy. We hypothesized that ... |
|
| Immunotherapeutic Cell-Based Vaccine to Combat Metastatic Breast Cancer |
JUL 2000 |
51 pages |
| Authors:
Beth Pulaski; S. O. Rosenbert; MARYLAND UNIV BALTIMORE
|
| Because metastases spread to many different organs and few animal models accurately reflect the clinical progression of metastatic disease, it has been difficult to develop effective therapies to specifically target these lesions. We analyzed the poorly immunogenic mouse 4T1 mammary carcinoma and demonstrated that it is an excellent model for human metastatic breast cancer. Primary 4T1 tumors displayed signs of edema, extension to the peritoneal lining, and ulcerations of the ... |
|
| The Role of Breast Cancer Derived Prostaglandin E2 in the Elaboration of a Therapeutic Immune Response |
JUL 2000 |
23 pages |
| Authors:
Stephen Eck; PENNSYLVANIA UNIV PHILADELPHIA
|
| The principal goal was to understand why breast cancer cells are able to evade the host immune system despite the presence of tumor antigens and tumor antigen-specific T lymphocytes. We had previously demonstrated that tumor- derived prostaglandin E2 (PGE2) directly contributes to the lack of a significant immune response to breast cancer cells. However, the production of PGE2 by breast cancer cells did not completely explain the immune suppressive effect ... |
|
| Target Antigens for Breast Cancer Vaccines |
JUL 2000 |
21 pages |
| Authors:
Ricardo Cibotti; VACCINEX L P ROCHESTER NY
|
| The prospects for development of well defined tumor vaccines has received great impetus from the demonstration that human melanoma express common antigens recognized by cytotoxic T cells (CTL). Although significant problems related to antigen delivery and immune stimulation remain to be resolved, the availability of molecularly defined breast tumor antigens would be a major step towards development of a vaccine for breast cancer. The most successful approaches to identify antigens ... |
|
| The Use of Her2/neu-Specific Genetic Vaccines for the Prevention and Treatment of Breast Cancer |
JUL 2000 |
8 pages |
| Authors:
Roland Tisch; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| We are investigating the feasibility of using HER2/neu encoding genetic vaccines to induce potent CD4+ and CD8+ T cell reactivity for the prevention and treatment of breast cancer. Two strategies of genetic vaccination, each with distinct advantages, will be assessed. The first strategy entails the use of alphavirus Venezuelan equine encephalitis virus (VEE)- replicons which selectively infect dendritic cells in vivo. Dendritic cells are characterized by a highly potent capacity ... |
|
| Prostate Tumor Antigen Discovery: Development of a Novel Genetic Approach |
JUL 2000 |
|
| Authors:
Dean L. Mann; Robert Malone; MARYLAND UNIV BALTIMORE
|
| Immunotherapy may provide an effective adjunct to current treatment modalities for prostate cancer. To achieve this goal, several fundamental immunologic questions need to be addressed. These include optimization of cellular immune responses to candidate tumor antigen and exploration of the extent to which HLA Class I and Class II diversity will restrict application of a candidate prostatic cancer vaccine. PSA was chosen as a candidate antigen for study and dendritic ... |
|
| Designer T Cells for Breast Cancer Therapy: Phase I Studies |
JUL 2000 |
76 pages |
| Authors:
Richard Junghans; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| In the present report we describe studies using several types of chimeric immune receptors. These receptors consist of an antibody fragment against the CEA tumor antigen joined to signaling portions of various T cell receptors (e.g., IgTCR, IgCD28, IgLFAi). The antibody fragment confers CEA specificity to the receptor, while the signaling domains transmit T cell activation and costimulation signals. These receptors allow the T cell ... |
|
| Characterization of New Breast Tumor-Specific Antigens Using a Novel Antigen Discovery System |
JUN 2000 |
|
| Authors:
Henry Kao; PITTSBURGH UNIV PA
|
| The goal of this project is to devise a new method for antigen discovery using dendritic cells as antigen-presenting cells to prime autologous naive CD4(+) and CD8(+) T cells from healthy donors against breast tumor proteins and peptides. To identify HLA Class I-restricted tumor antigens, we extracted peptides from tumor HLA Class I molecules, fractionated them by RP-HPLC, and loaded them onto DCs to prime naive CD8(+) T cells in ... |
|
| Tumor-Specific Immunotherapy of Mammary Cancer |
APR 2000 |
84 pages |
| Authors:
Suzanne Ostrand-Rosenberg; MARYLAND UNIV BALTIMORE COUNTY BALTIMORE MD
|
| For many patients with mammary cancer the primary tumor can be successfully treated by surgical removal, however the long-term prognosis is not favorable because of the high frequency of metastatic disease, which is not treatable by current approaches. Our goal is to develop vaccination strategies to minimize metastatic disease. We postulate that an improvement in the generation of mammary carcinoma-specific CD4+ T lymphocytes will facilitate development of CD8+ T cell ... |
|
| Investigation of Immune Function in Naval Marine Mammals |
21 MAR 2000 |
5 pages |
| Authors:
Tracy Romano; TEXAS A AND M UNIV COLLEGE STATION DEPT OF VETERINARY ANATOMY
|
| Marine mammals are used and maintained by the US Navy for military operations and research and development. Health maintenance is critical for optimal performance. However, very little is known about the immune system of marine mammals, especially the total aquatic cetaceans (dolphins, whales, and porpoises). This is due in part to obtaining access to animals and tissue samples as well as the lack of cetacean-specific ... |
|
| The Effects of a Nutrient-Enriched Bar on Host Defense Mechanisms and Immunogenicity of Hepatitis A Vaccine During US Army Ranger Training |
FEB 2000 |
53 pages |
| Authors:
Steven M. Wood; Jeffrey S. Kennedy; Ronald Shippee; Joanne Arsenault; ARMY RESEARCH INST OF ENVIRONMENTAL MEDICINE NATICK MA
|
| This study was designed to assess the effects of a nutritionally- enhanced food bar and intense, protracted stress as engendered by US Army Ranger training on immune function as measured by immunogenicity to Hepatitis A vaccine, leukocyte phenotype, and delayed type hypersensitivity reaction. The stress of Ranger training caused a number of immunological changes from baseline, and the group consuming the bar fortified with antioxidants, ... |
|
| Induction of Immunity to a Breast Cancer Associated Mucin in Transgenic Mice Expressing the Hurnan Antigen - A Preclinical Study |
OCT 1999 |
97 pages |
| Authors:
Edward P. Cohen; ILLINOIS UNIV AT CHICAGO
|
| The high incidence of breast cancer and the severity of the disease have created an urgent need for new and innovative forms of treatment. Mucin, the product of the MUC1 gene, has been identified as a breast cancer associated antigen in patients. We use a unique animal model of breast cancer to evaluate immunotherapeutic strategies to treat mice with the disease. Transgenic mice were prepared ... |
|
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