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Peptide Vaccines (peptide + vaccine)

Distribution by Scientific Domains

Medical Sciences	69%

Selected Abstracts

Immunization with a P53 synthetic long peptide vaccine induces P53-specific immune responses in ovarian cancer patients, a phase II trial,

INTERNATIONAL JOURNAL OF CANCER, Issue 9 2009
Ninke Leffers
Abstract The prognosis of ovarian cancer, the primary cause of death from gynecological malignancies, has only modestly improved over the last decades. Immunotherapy is one of the new treatment modalities explored for this disease. To investigate safety, tolerability, immunogenicity and obtain an impression of clinical activity of a p53 synthetic long peptide (p53-SLP) vaccine, twenty patients with recurrent elevation of CA-125 were included, eighteen of whom were immunized 4 times with 10 overlapping p53-SLP in Montanide ISA51. The first 5 patients were extensively monitored for toxicity, but showed no , grade 3 toxicity, thus accrual was continued. Overall, toxicity was limited to grade 1 and 2, mostly locoregional, inflammatory reactions. IFN-, producing p53-specific T-cell responses were induced in all patients who received all 4 immunizations as measured by IFN-, ELISPOT. An IFN-, secretion assay showed that vaccine-induced p53-specific T-cells were CD4+, produced both Th1 and Th2 cytokines as analyzed by cytokine bead array. Notably, Th2 cytokines dominated the p53-specific response. P53-specific T-cells were present in a biopsy of the last immunization site of at least 9/17 (53%) patients, reflecting the migratory capacity of p53-specific T-cells. As best clinical response, stable disease evaluated by CA-125 levels and CT-scans, was observed in 2/20 (10%) patients, but no relationship was found with vaccine-induced immunity. This study shows that the p53-SLP vaccine is safe, well tolerated and induces p53-specific T-cell responses in ovarian cancer patients. Upcoming trials will focus on improving T helper-1 polarization and clinical efficacy. © 2009 UICC [source]

A peptide derived from hepatitis C virus (HCV) core protein inducing cellular responses in patients with HCV with various HLA class IA alleles,

JOURNAL OF MEDICAL VIROLOGY, Issue 7 2009
Yamei Niu
Abstract C35-44 peptide is a well known HLA-A2-restricted CTL epitope originating from hepatitis C virus (HCV) core protein. It was reported that the majority of HCV positive patients had significant levels of serum IgG specific to this peptide. This study addressed whether C35-44 peptide could induce CTL activity restricted to various HLA class IA alleles or could not. This peptide demonstrated binding activity to HLA-A*2402, -A*2601, -A*3101, and -A*3303 molecules, but not to HLA-A*1101 by means of stabilization assay. This peptide also induced CTL activity restricted to each of them, except HLA-A11+ peripheral blood mononuclear cells from HCV 1b+ patients by means of 51Cr-release assay. With regard to HLA-A2 subtypes, this peptide demonstrated binding activity to HLA-A*0201 and -A*0206, but not to -A*0207 molecules. Furthermore, this peptide induced CTL activity from both the patients and healthy donors with all the HLA class IA molecules mentioned above by means of interferon-, production assay. These results may provide new insights for the development of a novel peptide vaccine against HCV compatible with various HLA class IA types. J. Med. Virol. 81:1232,1240, 2009. © 2009 Wiley-Liss, Inc. [source]

Validation of a solid-phase-bound steroid scaffold for the synthesis of novel cyclic peptidosteroids,

JOURNAL OF PEPTIDE SCIENCE, Issue 11 2007
Catherine A. Bodé
Abstract The current article reports on the synthesis of a new type of cyclic peptidosteroid, in which a bile-acid-based scaffold was used for the conformational restriction of a loop-like peptide. Convergent coupling of two tetrapeptides to the non-peptidic steroidal entity was carried out once in the classical C-to-N and once in the non-classical N-to-C direction. Peptide backbone cyclisation was then carried out, giving rise to a ring size equivalent to approximately 12 amino acids. This type of construct will be used in the development of a peptide vaccine against measles. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source]

Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer

CANCER SCIENCE, Issue 2 2010
Motoki Miyazawa
Vascular endothelial growth factor receptor 2 (VEGFR2) is an essential factor in tumor angiogenesis and in the growth of pancreatic cancer. Immunotherapy using epitope peptide for VEGFR2 (VEGFR2-169) that we identified previously is expected to improve the clinical outcome. Therefore, a phase I clinical trial combining of VEGFR2-169 with gemcitabine was conducted for patients with advanced pancreatic cancer. Patients with metastatic and unresectable pancreatic cancer were eligible for the trial. Gemcitabine was administered at a dose of 1000 mg/m2 on days 1, 8, and 15 in a 28-day cycle. The VEGFR2-169 peptide was subcutaneously injected weekly in a dose-escalation manner (doses of 0.5, 1, and 2 mg/body, six patients/one cohort). Safety and immunological parameters were assessed. No severe adverse effect of grade 4 or higher was observed. Of the 18 patients who completed at least one course of the treatment, 15 (83%) developed immunological reactions at the injection sites. Specific cytotoxic T lymphocytes (CTL) reacting to the VEGFR2-169 peptide were induced in 11 (61%) of the 18 patients. The disease control rate was 67%, and the median overall survival time was 8.7 months. This combination therapy for pancreatic cancer patients was tolerable at all doses. Peptide-specific CTL could be induced by the VEGFR2-169 peptide vaccine at a high rate, even in combination with gemcitabine. From an immunological point of view, the optimal dose for further clinical trials might be 2 mg/body or higher. This trial was registered with ClinicalTrial.gov (no. NCT 00622622). (Cancer Sci 2009) [source]

Personalized peptide vaccines: A new therapeutic modality for cancer

CANCER SCIENCE, Issue 10 2006
Kyogo Itoh
Therapeutic cancer vaccines have enjoyed little success so far, although many clinical trials have been conducted. Therefore, the creation of new protocols capable of inducing an objective response is required. We examined two of these protocols in the present review. The first is a personalized protocol to take into account the immunological diversity of cytotoxic T lymphocyte responses among patients. The second is a combination therapy designed to adapt to the presence of major histocompatibility complex (MHC)-loss cancer cells. The objective response rates of our classical (non-personalized) peptide vaccines were 0%, whereas that of personalized vaccines was 11.1% in the total advanced cancers and ,20% in malignant glioma and cervical cancers, respectively. A ,50% decrease in serum prostate-specific antigen (PSA) was seen in 8.7% of advanced hormone refractory prostate cancer patients by personalized vaccination alone, whereas such a decrease was seen in 54% of patients when the personalized vaccination was combined with a low dose of estramustine. Based on these experiences, we propose a personalized peptide vaccine combined with chemotherapy as a new treatment modality for cancers. (Cancer Sci 2006; 97: 970,976) [source]

The hinge region fragment of immunoglobulin G improves immunogenicity of recombinant gonadotrophin-releasing hormone conjugated to the T-helper epitope in designing peptide vaccines

IMMUNOLOGY, Issue 1pt2 2009
Jinshu Xu
Summary In our previous study, the hinge fragment (225,232/225,,232,) of human immunoglobulin G1 (IgG1) was used as a space peptide linker for synthesizing the GnRH3,hinge,MVP chimeric peptide, whereby three repeated gonadotrophin-releasing hormone (GnRH) units and a T-cell epitope from measles virus fusion protein (MVP) were amide-bond-linked at the N and C terminus, respectively, to the hinge peptide for producing anti-GnRH antibody responses. To investigate whether or not the hinge region fragment can improve the immunogenicity of GnRH, we further synthesized and purified GnRH3,hinge,MVP, GnRH3,hinge and GnRH3,MVP using recombinant DNA technology. Under high pH conditions, GnRH3,hinge,MVP was capable of forming double-chain structures. Immunization of male mice with the immunogens of GnRH3,hinge,MVP resulted in the generation of high-titre antibodies specific for GnRH. The synthetic GnRH3,hinge and GnRH3,MVP induced a lower titre of anti-GnRH antibody than GnRH3,hinge,MVP. This was followed by a decrease in serum testosterone levels, which resulted in a low level of expression of the relaxin-like factor gene in the testis. Our data suggest that peptide and T-cell epitopes oriented at the N-terminus or C-terminus of hinge peptides simplify the antigenic peptide conjugates and may be considered as potential synthetic immunogens. [source]

CD40-mediated enhancement of immune responses against three forms of influenza vaccine

IMMUNOLOGY, Issue 1 2007
Caterina Hatzifoti
Summary There is potential for influenza A infections to cause massive morbidity and mortality. Vaccination may be the primary defence against pandemic influenza, and potential pandemic'flu vaccines may be produced conventionally, in embryonated eggs, or as recombinant protein or synthetic peptide vaccines. However the vaccines are produced, the supply may be limiting, and it will be important to enhance the immunogenicity of the vaccines as much as possible. We have shown that conjugation to CD40 binding antibody is a very efficient way of enhancing immune responses against model antigens, but were interested in assessing the effectiveness of this system using influenza vaccines. We produced conjugates of CD40 monoclonal antibody (mAb) and isotype control with three potential influenza vaccines: a peptide-based vaccine containing T- and B-cell epitopes from virus haemagglutinin; a whole, killed virus vaccine; and a commercially produced split virus vaccine. CD40 mAb conjugates in each case were more immunogenic, but the adjuvant effect of CD40 conjugation was greatest with the split vaccine, where antibody responses were enhanced by several hundred-fold after a single immunization, and lymphocyte proliferation in response to antigen in vitro was also strongly enhanced. [source]

Viral peptide immunogens: current challenges and opportunities

JOURNAL OF PEPTIDE SCIENCE, Issue 12 2007
Ali Azizi
Abstract Synthetic peptide vaccines have potential to control viral infections. Successful experimental models using this approach include the protection of mice against the lethal Sendai virus infection by MHC class I binding CTL peptide epitope. The main benefit of vaccination with peptide epitopes is the ability to minimize the amount and complexity of a well-defined antigen. An appropriate peptide immunogen would also decrease the chance of stimulating a response against self-antigens, thereby providing a safer vaccine by avoiding autoimmunity. In general, the peptide vaccine strategy needs to dissect the specificity of antigen processing, the presence of B-and T-cell epitopes and the MHC restriction of the T-cell responses. This article briefly reviews the implications in the design of peptide vaccines and discusses the various approaches that are applied to improve their immunogenicity. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source]

Personalized peptide vaccines: A new therapeutic modality for cancer

Developments in allergen-specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen-specific immunoglobulin E and T cell reactivity

CLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2010
M. Focke
Summary Allergen-specific immunotherapy (SIT) is the only specific and disease-modifying approach for the treatment of allergy but several disadvantages have limited its broad applicability. We argue that the majority of the possible disadvantages of SIT such as unwanted effects, poor efficacy and specificity as well as inconvenient application are related to the poor quality of natural allergen extracts, which are the active ingredients of all currently available allergy vaccines. Because of the progress made in the field of molecular allergen characterization, new allergy vaccines based on recombinant allergens, recombinant hypoallergenic allergen derivatives and allergen-derived T cell peptides have entered clinical testing and hold promise to reduce the side-effects and to increase the specificity as well as the efficacy of SIT. Here, we present a refined immunotherapy concept, which is based on the use of peptides derived from allergen surfaces that exhibit reduced, allergen-specific IgE as well as T cell reactivity. These peptides when fused to non-allergenic carriers give rise to allergen-specific protective IgG responses with T cell help from a non-allergenic carrier molecule. We summarize the experimental data demonstrating that such peptide vaccines can bypass allergen-specific IgE as well as T cell activation and may be administered at high doses without IgE- and T cell-mediated side-effects. Should these peptide vaccines prove efficacious and safe in clinical trials, it may become possible to develop convenient, safe and broadly applicable forms of SIT as true alternatives to symptomatic, drug-based allergy treatment. Cite this as: M. Focke, I. Swoboda, K. Marth and R. Valenta, Clinical & Experimental Allergy, 2010 (40) 385,397. [source]