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: 7122673
• 负责人: JOSEPH Wayne FAY
• 金额: $ 10.09万
• 依托单位: BAYLOR RESEARCH INSTITUTE
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/7122673
• 关键词: CD34 molecule; antineoplastics; biotechnology; cellular immunity; clinical trial phase I; clinical trial phase II; combination cancer therapy; cyclophosphamide; cytotoxic T lymphocyte; dendritic cells; helper T lymphocyte; hematopoietic stem cells; human subject; human therapy evaluation; immune response; immunomodulators; immunosuppressive; melanoma; neoplasm /cancer chemotherapy; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; patient oriented research; tumor antigens; vaccine development; vaccine evaluation

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).

CD34+来源树突状细胞（dc）转移性黑色素瘤患者的HLA-A*201疫苗接种