Conditioning Patients to Increase DC-vaccine Potency
对患者进行调理以提高 DC 疫苗的效力
基本信息
- 批准号:7122673
- 负责人:
- 金额:$ 10.09万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-03-01 至 2009-05-31
- 项目状态:已结题
- 来源:
- 关键词:CD34 moleculeantineoplasticsbiotechnologycellular immunityclinical trial phase Iclinical trial phase IIcombination cancer therapycyclophosphamidecytotoxic T lymphocytedendritic cellshelper T lymphocytehematopoietic stem cellshuman subjecthuman therapy evaluationimmune responseimmunomodulatorsimmunosuppressivemelanomaneoplasm /cancer chemotherapyneoplasm /cancer immunologyneoplasm /cancer immunotherapyneoplasm /cancer vaccinepatient oriented researchtumor antigensvaccine developmentvaccine evaluation
项目摘要
Vaccination of HLA-A*201 patients with metastatic melanoma with dendritic cells (DCs) derived from CD34+
hematopoietic cell progenitor cells (CD34+HPCs) loaded with melanoma peptide antigens, KLH and flu
peptide resulted in the induction of CD8+ T cell immunity to melanoma peptides and some clinical benefit.
Immunity was measured by the production of interferon-gamma in the presence of melanoma peptides and
control antigens by CD8+ T cells obtained from blood. T cell immunity correlated with early clinical outcome
and survival. Patients who progressed early had either no T cell immunity or transient T cell immunity to DC
vaccination. There may be several reasons for the absence of DC-induced CD8+ T cell immunity in these
patients including: the inability of DCs to prime T cells against tumor antigens, the presence of tumor
specific tolerance induced by host suppressor lymphocytes, and an insufficient anti-melanoma T cell
repertoire. AIM 1 will determine whether pre-treatment of patients with stage IV melanoma with CPA
improves the immune and clinical response after DC vaccination. We will carry out a phase l/ll randomized
clinical trial in patients with stage IV melanoma who will receive either placebo or CPA (500mg/m2) followed
by vaccination with CD34-DCs pulsed with melanoma peptides and KLH. As a control, a separate aliquot of
DCs will be pulsed with HIV peptides as neoantigens that will be mixed with the peptide-loaded DCs and
administered at the same time. The primary outcome is the induction of melanoma-specific CD8+T cell
immunity. The secondary outcome is the rate of objective clinical responses. Tertiary outcomes are:
reduction of regulatory/suppressor CD4+T cells (AIM 2) and priming of HIV-specific CD8+T cells (AIM 3).
用来源于CD 34+的树突状细胞(DC)接种患有转移性黑素瘤的HLA-A*201患者
加载有黑素瘤肽抗原、KLH和流感病毒的造血细胞祖细胞(CD 34 + HPC)
肽导致对黑素瘤肽的CD 8 + T细胞免疫的诱导和一些临床益处。
免疫力通过在黑素瘤肽存在下干扰素-γ的产生来测量,
通过从血液中获得的CD 8 + T细胞控制抗原。T细胞免疫与早期临床结局相关
和生存早期进展的患者要么没有T细胞免疫,要么对DC有短暂的T细胞免疫
预防针在这些受试者中,DC诱导的CD 8 + T细胞免疫的缺乏可能有几个原因。
包括:DC不能针对肿瘤抗原引发T细胞,肿瘤细胞的存在,
宿主抑制性淋巴细胞诱导的特异性耐受和抗黑色素瘤T细胞不足
保留曲目。目的1将确定是否与CPA的IV期黑色素瘤患者的预治疗
改善DC疫苗接种后的免疫和临床应答。我们将进行I/II期随机
IV期黑色素瘤患者接受安慰剂或CPA(500 mg/m2)的临床试验,
通过用黑素瘤肽和KLH脉冲的CD 34-DC接种。作为对照,将单独等分的
DC将用作为新抗原的HIV肽脉冲,所述新抗原将与负载肽的DC混合,
同时管理。主要结果是黑色素瘤特异性CD 8 +T细胞的诱导
免疫力次要结局是客观临床应答率。三级结局为:
减少调节/抑制性CD 4 +T细胞(AIM 2)和引发HIV特异性CD 8 +T细胞(AIM 3)。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JOSEPH Wayne FAY其他文献
JOSEPH Wayne FAY的其他文献
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{{ truncateString('JOSEPH Wayne FAY', 18)}}的其他基金
Conditioning Patients to Increase DC-vaccine Potency
对患者进行调理以提高 DC 疫苗的效力
- 批准号:
7631317 - 财政年份:2000
- 资助金额:
$ 10.09万 - 项目类别:
Conditioning Patients to Increase DC-vaccine Potency
对患者进行调理以提高 DC 疫苗的效力
- 批准号:
7460927 - 财政年份:
- 资助金额:
$ 10.09万 - 项目类别:
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