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Optimization of Peptide Based Vaccines for Cancer

基于肽的癌症疫苗的优化

基本信息

批准号：
7491582
负责人：
Esteban Celis
金额：
$ 25.84万
依托单位：
H. LEE MOFFITT CANCER CTR & RES INST
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7491582
关键词：
Accounting Address Adjuvant Adoptive Cell Transfers Affect Alleles Animals Antigens Apoptosis Autoimmune Process Autoimmunity Biological Models CD4 Positive T Lymphocytes Cell Death Cells Clinic Cyclophosphamide Cytotoxic T-Lymphocytes Daily Data Dendritic Cells Development Disease Disease regression Disruption Dose Double-Stranded RNA Drug Formulations Emulsions Epitopes Family member Generations Genetic Engineering Helper-Inducer T-Lymphocyte Homeostasis Human Immune Immune Tolerance Immune response Immune system Immunity Immunization Infection Injection of therapeutic agent Lead Ligands Longevity Lymphocyte Lymphocyte Function Lymphokines Malignant - descriptor Malignant Neoplasms Mediating Memory Methods Mineral Oil Molecular Montanide ISA-51 Myelogenous Normal tissue morphology Numbers Pathology Pattern Peptide Signal Sequences Peptide Vaccines Peptides Personal Satisfaction Phase Play Poly I-C Relative (related person)Research Personnel Resistance Role Signal Transduction Site Subunit Vaccines T-Lymphocyte T-Lymphocyte Epitopes TLR9 gene Time Toll-like receptors Translations Tumor Antigens Tumor Immunity Vaccination Vaccines Water Week Withdrawal Work base cancer immunotherapy cancer prevention cell transformation cost effective cytotoxic design human TLR3 protein human study immunogenic immunogenicity in vivo incomplete Freund&apos s adjuvant lymph nodes pathogen peptide based vaccine prevent programs research study response size stem synthetic peptide tumor tumor growth vaccine evaluation

项目摘要

Optimization of Peptide Based Vaccines for Cancer. The successful identification of numerous T cell epitopes derived from tumor-associated antigens has opened the doors to the development of subunit vaccines for the treatment and prevention of cancer. Vaccines prepared from synthetic peptides representinc these T cell epitopes constitute an attractive approach for the induction of anti-tumor immune responses because they are easily manufactured, they are simple to characterize, they are relatively stable and most importantly, they are extremely cost effective as compared to other types of vaccines. However, peptide- based vaccines are not very immunogenic and so far the results in the clinic have been somewhat disappointing. We hypothesize that peptide vaccines fail to induce the robust T cell responses that are required to attain anti-tumor effects, because they lack the "danger signals" necessary that awaken the immune system. Moreover, most peptide vaccines tested so far have been designed to stimulate cytotoxic T lymphocytes (CTL) and have overlooked to trigger anti-tumor helper T lymphocyte (HTL) responses, which we believe are necessary for the persistence of anti-tumor CTL function at the tumor site (secondary hypothesis). In order to address these issues we propose to explore in an animal tumor model system the following specific aims : 1) To evaluate various vaccine formulations and adjuvants for their capacity to elicit CTL and HTL responses against peptide immunogens; 2) To assess the possibility of enhancing anti-tumor T cell responses induced by peptide vaccination, by disrupting lymphocyte homeostasis; and 3) To study the role of antigen-specific HTL in the survival and proliferative capacity of effector and memory CTL responses against tumors. To accomplish these aims we have selected compounds and experimental approaches that could be applied to human trials in an expedient manner. The completion of these studies should markedly facilitate the translation of effective peptide vaccines into the clinic.

肿瘤多肽疫苗的优化研究成功鉴定了大量T细胞

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Designing therapeutic cancer vaccines by mimicking viral infections.

DOI：
10.1007/s00262-016-1834-5
发表时间：
2017-02
期刊：
CANCER IMMUNOLOGY IMMUNOTHERAPY
影响因子：
5.8
作者：
Sultan, Hussein;Fesenkova, Valentyna I.;Addis, Diane;Fan, Aaron E.;Kumai, Takumi;Wu, Juan;Salazar, Andres M.;Celis, Esteban
通讯作者：
Celis, Esteban

Autophagy induced by conventional chemotherapy mediates tumor cell sensitivity to immunotherapy.

DOI：
10.1158/0008-5472.can-12-2236
发表时间：
2012-11-01
期刊：
Cancer research
影响因子：
11.2
作者：
Ramakrishnan R;Huang C;Cho HI;Lloyd M;Johnson J;Ren X;Altiok S;Sullivan D;Weber J;Celis E;Gabrilovich DI
通讯作者：
Gabrilovich DI

CCL17 and CCL22/CCR4 signaling is a strong candidate for novel targeted therapy against nasal natural killer/T-cell lymphoma.

DOI：
10.1007/s00262-015-1675-7
发表时间：
2015-06
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
0
作者：
Kumai T;Nagato T;Kobayashi H;Komabayashi Y;Ueda S;Kishibe K;Ohkuri T;Takahara M;Celis E;Harabuchi Y
通讯作者：
Harabuchi Y

STING activator c-di-GMP enhances the anti-tumor effects of peptide vaccines in melanoma-bearing mice.