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Cancer vaccine therapy with HLA-A24 restricted epitope peptide cocktail for patients with advanced metastatic colorectal cancer. Phase I/II clinical trial.

ABSTRACT: Interventions: Subcutaneous injection of cancer vaccine (seven peptides) Primary outcome(s): Safty Immunological response (in vitro CTL induction) Study Design: Single arm Non-randomized

DISEASE(S): Advanced Metastatic Colorectal Cancers

PROVIDER: 2620402 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Cancer vaccine therapy with HLA-A24 restricted epitope peptide cocktail for patients with advanced metastatic colorectal cancer. Phase I/II clinical trial.

Project description:Interventions: Subcutaneous injection of cancer vaccine (seven peptides) Primary outcome(s): Safty Immunological response (in vitro CTL induction) Study Design: Single arm Non-randomized

| 2621744 | ecrin-mdr-crc

Phase I/II clinical trial of HLA-A24 restricted epitope peptide cocktail therapy with UFT+LV for patients with advanced metastatic colorectal cancer.

Project description:Interventions: Subcutaneous injection of cancer vaccine (seven peptides) UFT+LV Primary outcome(s): Safty Immunological response (in vitro CTL induction) Study Design: Single arm Non-randomized

| 2623214 | ecrin-mdr-crc

Cancer specific vaccine therapy using HLA-A24 restricted epitope-peptide for patients with advanced metastatic colorectal cancer.PhaseI/II clinical trial.

Project description:Interventions: Subctaneus injection of cancer peptide vaccine(three peptides) Primary outcome(s): Safety Overall survival Study Design: Single arm Non-randomized

| 2620437 | ecrin-mdr-crc

WT1 Trio Peptide-vaccine for Rare Cancers

Project description:Interventions: A patient is vaccinated with Montanide ISA51-adjuvanted WT1 Trio cancer vaccine consisting of two WT1 CTL peptides (WT1-126 and WT1-235) and one WT1 HTL peptide (WT1-332) (2mg each) seven times at the interval of two weeks. Primary outcome(s): Induction of WT1-specific immune responses assessed by WT1-related tests such as WT1-DTH skin reaction and serum levels of WT1 peptide IgG autoantibody at 1M, 2M, and 3M of WT1 Trio vaccine. Study Design: Single arm Non-randomized

| 2638832 | ecrin-mdr-crc

Identification of an HLA-A2-restricted epitope peptide derived from hypoxia-inducible protein 2 (HIG2).

Project description:We herein report the identification of an HLA-A2 supertype-restricted epitope peptide derived from hypoxia-inducible protein 2 (HIG2), which is known to be a diagnostic marker and a potential therapeutic target for renal cell carcinoma. Among several candidate peptides predicted by the HLA-binding prediction algorithm, HIG2-9-4 peptide (VLNLYLLGV) was able to effectively induce peptide-specific cytotoxic T lymphocytes (CTLs). The established HIG2-9-4 peptide-specific CTL clone produced interferon-γ (IFN-γ) in response to HIG2-9-4 peptide-pulsed HLA-A*02:01-positive cells, as well as to cells in which HLA-A*02:01 and HIG2 were exogenously introduced. Moreover, the HIG2-9-4 peptide-specific CTL clone exerted cytotoxic activity against HIG2-expressing HLA-A*02:01-positive renal cancer cells, thus suggesting that the HIG2-9-4 peptide is naturally presented on HLA-A*02:01 of HIG-2-expressing cancer cells and is recognized by CTLs. Furthermore, we found that the HIG2-9-4 peptide could also induce CTLs under HLA-A*02:06 restriction. Taken together, these findings indicate that the HIG2-9-4 peptide is a novel HLA-A2 supertype-restricted epitope peptide that could be useful for peptide-based immunotherapy against cancer cells with HIG2 expression.

| S-EPMC3885709 | biostudies-literature

Long-term maintenance of anti-tumor immune responses by vaccination with tri-WT1 peptide cancer vaccine WT1 Trio

Project description:Interventions: A patient is vaccinated with Montanide ISA51-adjuvanted WT1 Trio cancer vaccine consisting of two WT1 CTL peptides (WT1-126 and WT1-235) and one WT1 HTL peptide (WT1-332) (2mg each) seven times at the interval of two to four weeks. The interval can be changed within a range from one to 16 weeks. Primary outcome(s): Induction of WT1-specific immune responses assessed by WT1-related tests such as WT1-DTH skin reaction, serum levels of WT1 peptide IgG autoantibody, and frequency of WT1-CTL in PB * This is evaluated at the interval ranging from 6 to 12 months. Study Design: Single arm Non-randomized

| 2638831 | ecrin-mdr-crc

Transcription profiling and proteomic profiling of human B-LCL cell lines (TAP1/2 +/+ and TAP1/2 -/-) to analyse HLA peptide repertoire

Project description:The TAP transporter is responsible for transferring cytosolic peptides into the ER where they can be loaded onto MHC molecules. Deletion of TAP results in a drastic reduction of MHC surface expression and alters the presented peptide pattern. Using the TAP deficient cell line LCL721.174 and its TAP expressing progenitor cell line LCL721.45, we have identified and quantified more than 160 HLA ligands, 50 out of which were presented TAP independently. Peptides which were predominantly presented on the TAP deficient LCL721.174 cell line had a decreased MHC binding affinity according to their SYFPEITHI and BIMAS score. About half of the identified TAP independently presented peptides were not derived from signal sequences and may partly be generated by the proteasome. Furthermore, we have excluded that different HLA presentation ratios were due to varying expression of the respective protein or due to changes in the antigen loading complex. Features of TAP-independently presented peptides as well as proteasomal contribution to their generation provides an insight into basic immunological mechanisms. Experiment Overall Design: Two B-LCL cell lines (TAP1/2 +/+ and TAP1/2 -/-) were compared in their gene and protein expression as well as in their HLA peptide repertoire

2008-06-16 | E-GEOD-9437 | biostudies-arrayexpress

Histocompatibility Leukocyte Antigen (HLA)-A*0201 Restricted Peptide Vaccine Therapy in Patients With Colorectal Cancer

Project description:The purpose of this study is to evaluate the safety and time to progression of HLA-A*0201 restricted epitope peptides VEGFR1 and VEGFR2 emulsified with Montanide ISA 51 in combination with Tegafur/Uracil/Folinate chemotherapy.

| 2055367 | ecrin-mdr-crc

Histocompatibility Leukocyte Antigen (HLA)-A*2402 Restricted Peptide Vaccine Therapy in Patients With Colorectal Cancer

Project description:The purpose of this study is to evaluate the safety and time to progression of HLA-A*2402 restricted epitope peptides RNF43, TOMM34, VEGFR1 and VEGFR2 emulsified with Montanide ISA 51 in combination with Tegafur/Uracil/Folinate chemotherapy.

| 2055342 | ecrin-mdr-crc

Promiscuous Recognition of a Trypanosoma cruzi CD8+ T Cell Epitope among HLA-A2, HLA-A24 and HLA-A1 Supertypes in Chagasic Patients.

Project description:BackgroundTcTLE is a nonamer peptide from Trypanosoma cruzi KMP-11 protein that is conserved among different parasite strains and that is presented by different HLA-A molecules from the A2 supertype. Because peptides presented by several major histocompatibility complex (MHC) supertypes are potential targets for immunotherapy, the aim of this study was to determine whether MHC molecules other than the A2 supertype present the TcTLE peptide.Methodology/principal findingsFrom 36 HLA-A2-negative chagasic patients, the HLA-A genotypes of twenty-eight patients with CD8+ T cells that recognized the TcTLE peptide using tetramer (twenty) or functional (eight) assays, were determined. SSP-PCR was used to identify the A locus and the allelic variants. Flow cytometry was used to analyze the frequency of TcTLE-specific CD8+ T cells, and their functional activity (IFN-γ, TNFα, IL-2, perforin, granzyme and CD107a/b production) was induced by exposure to the TcTLE peptide. All patients tested had TcTLE-specific CD8+ T cells with frequencies ranging from 0.07-0.37%. Interestingly, seven of the twenty-eight patients had HLA-A homozygous alleles: A*24 (5 patients), A*23 (1 patient) and A*01 (1 patient), which belong to the A24 and A1 supertypes. In the remaining 21 patients with HLA-A heterozygous alleles, the most prominent alleles were A24 and A68. The most common allele sub-type was A*2402 (sixteen patients), which belongs to the A24 supertype, followed by A*6802 (six patients) from the A2 supertype. Additionally, the A*3002/A*3201 alleles from the A1 supertype were detected in one patient. All patients presented CD8+ T cells producing at least one cytokine after TcTLE peptide stimulation.Conclusion/significanceThese results show that TcTLE is a promiscuous peptide that is presented by the A24 and A1 supertypes, in addition to the A2 supertype, suggesting its potential as a target for immunotherapy.

| S-EPMC4790940 | biostudies-literature

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