Immunotherapeutic Approaches to Cancer Treatment

癌症治疗的免疫治疗方法

• 批准号: 7405191
• 负责人: RICHARD B ALEXANDER
• 金额: $ 12.36万
• 依托单位: VIROGENOMICS, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-02 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7405191
• 关键词: Address; Antibodies; Antigen Targeting; Antigens; Autoantigens; Biological Assay; CD4 Positive T Lymphocytes; CD8B1 gene; Cancer Vaccines; Carrying Capacities; Cells; Characteristics; Clinical; Clinical Research; Communicable Diseases; Cytomegalovirus; DNA; Data; Development; Disease; Engineering; Epitopes; Freund' s Adjuvant; Goals; Granulomatous Prostatitis; HIV; HLA Antigens; Human; Immune; Immune response; Immunotherapeutic agent; Immunotherapy; Individual; Infection; Inflammatory; Influenza; Interferons; Laboratories; Life; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Modeling; Mus; Numbers; Patients; Peptides; Pertussis Toxin; Phase; Population; Process; Prostate; Prostate-Specific Antigen; Publishing; Purpose; Rate; Reagent; Recombinants; Series; Serum; Spleen; T memory cell; T-Lymphocyte; T-Lymphocyte Epitopes; Tandem Repeat Sequences; Technology; Testing; Tumor Antigens; Vaccinated; Vaccination; Vaccines; Vaccinia virus; Viral; Virus; Work; base; cancer immunotherapy; cancer regression; cancer therapy; enzyme linked immunospot assay; immunogenic; immunogenicity; in vivo; lymph nodes; men; mouse model; research study; response; tumor; tumor immunology; vaccination strategy; vector; vector-induced

DESCRIPTION (provided by applicant): Immunotherapy as a treatment for cancer has been intensely investigated, but few studies have resulted in meaningful clinical responses. Many fundamental principals of tumor immunology have been clarified in recent years with the recognition and description of many antigens in tumors that can be recognized by T lymphocytes. Vaccination strategies to induce an immune response against these tumor antigens have also been developed and shown to induce a T cell response in patients. However, studies showing an objective response of cancer regression following vaccination are limited in number. One explanation for this minimal response rate is that the immunogenicity of the vaccines used for these trials in humans is too low to induce a response of sufficient magnitude to result in cancer regression. The long-term goal of this project is to determine the utility of recombinant cytomegalovirus (rCMV)-based vaccines for systemic immunotherapy for cancer. Human CMV (hCMV) is a highly immunogenic virus that results in persistent, life-long infection in the human host. About half of the U.S. population has been exposed to hCMV infection as demonstrated by the finding of antibodies to defined viral epitopes in the serum (seropositive). The virus has unique characteristics as a vaccine including: 1) lack of disease associated with hCMV infection in the immune-normal host, 2) ability to re-infect hCMV-seropositive individuals, 3) large carrying capacity for heterologous DNA, 4) life-long persistence within the host corresponding to 5) induction of a large immune response (10-20% of both the CD4+ and CD8+ memory T cells directed against hCMV antigens in asymptomatically infected individuals). Such rCMV-based vaccines expressing defined heterologous target antigens are being developed and have promise as vaccines for infectious disease such as influenza and HIV. The purpose of this proposal is to extend these observations to determine the capacity of CMV-based vectors expressing cancer-associated target antigens as an immunotherapy for cancer.Immunotherapy as a treatment for cancer has been intensely investigated, but few studies have resulted in meaningful clinical responses. The purpose of this proposal is to determine the capacity of CMV-based vectors expressing cancer-associated target antigens as an immunotherapy for cancer.

描述（由申请人提供）：免疫疗法作为癌症治疗方法已得到深入研究，但很少有研究产生有意义的临床反应。近年来，随着肿瘤中许多可被 T 淋巴细胞识别的抗原的识别和描述，肿瘤免疫学的许多基本原理已得到阐明。诱导针对这些肿瘤抗原的免疫反应的疫苗接种策略也已被开发出来，并被证明可以诱导患者的 T 细胞反应。然而，显示疫苗接种后癌症消退的客观反应的研究数量有限。对于这种最低反应率的一种解释是，用于这些人体试验的疫苗的免疫原性太低，无法诱导足够程度的反应来导致癌症消退。该项目的长期目标是确定基于重组巨细胞病毒（rCMV）的疫苗在癌症全身免疫治疗中的效用。人类巨细胞病毒 (hCMV) 是一种高免疫原性病毒，可导致人类宿主持续终生感染。血清中发现针对特定病毒表位的抗体（血清阳性）证明，大约一半的美国人曾感染过 hCMV。该病毒作为疫苗具有独特的特征，包括：1) 免疫正常宿主中不存在与 hCMV 感染相关的疾病，2) 能够重新感染 hCMV 血清阳性个体，3) 异源 DNA 携带能力大，4) 寿命-在宿主体内长期持续存在，相当于 5) 诱导大量免疫反应（无症状感染者中 10-20% 的 CD4+ 和 CD8+ 记忆 T 细胞针对 hCMV 抗原）个人）。这种表达特定异源靶抗原的基于 rCMV 的疫苗正在开发中，有望成为流感和 HIV 等传染病的疫苗。该提案的目的是扩展这些观察结果，以确定表达癌症相关靶抗原的基于 CMV 的载体作为癌症免疫疗法的能力。免疫疗法作为癌症治疗方法已得到深入研究，但很少有研究产生有意义的临床结果回应。该提案的目的是确定基于 CMV 的载体表达癌症相关靶抗原作为癌症免疫疗法的能力。

项目成果

A cytomegalovirus-based vaccine expressing a single tumor-specific CD8+ T-cell epitope delays tumor growth in a murine model of prostate cancer.

一种表达单一肿瘤特异性 CD8 T 细胞表位的基于巨细胞病毒的疫苗可延迟前列腺癌小鼠模型中的肿瘤生长。

• 发表时间: 2012-06
• 作者: Klyushnenkova, Elena N;Kouiavskaia, Diana V;Parkins, Christopher J;Caposio, Patrizia;Botto, Sara;Alexander, Richard B;Jarvis, Michael A
• 通讯作者: Jarvis, Michael A