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
• 负责人: JOSEPH Wayne FAY
• 金额: $ 19.74万
• 依托单位: BAYLOR RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7631317
• 关键词: Address; Aliquot; Antigens; Biological Assay; Blood; Blood specimen; CD34 gene; CD4 Positive T Lymphocytes; CD8 Antigens; CD8B1 gene; CXCR3 gene; Cells; Clinical; Clinical Trials; Clinical effectiveness; Cyclophosphamide; Dendritic Cell Vaccine; Dendritic Cells; Disease Progression; Failure; Flow Cytometry; Flu matrix protein; HIV; Hematopoietic; IL2RA gene; Immune; Immune response; Immune system; Immunity; Immunotherapy; Influenza; Integration Host Factors; Interferon Type II; Interleukin-10; Keyhole Limpet Hemocyanin; Lymphocyte; Measures; Metastatic Melanoma; Monitor; Outcome; Patients; Peptides; Phase; Phenotype; Physiologic pulse; Placebos; Principal Investigator; Production; Progressive Disease; Pulse taking; Randomized Clinical Trials; Rate; Regulation; Research; Staging; Stem cells; Suppressor-Effector T-Lymphocytes; T-Lymphocyte; Technology; Testing; Therapeutic; Time; Tumor Antigens; Vaccination; Vaccine Antigen; Vaccines; conditioning; flu; immunogenicity; improved; in vivo; melanoma; programs; research study; response; tumor

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+来源的树突状细胞免疫人类白细胞抗原-A*201转移性黑色素瘤患者 CD34+造血祖细胞(CD34+HPC)负载黑色素瘤多肽抗原、KLH和Flu 多肽在诱导CD8+T细胞对黑色素瘤多肽的免疫方面具有一定的临床应用价值。 免疫力是通过在黑色素瘤多肽和 通过从血液中获取的CD8+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没有一过性T细胞免疫 接种疫苗。这些患者缺乏DC诱导的CD8+T细胞免疫可能有几个原因 患者包括：DC不能激活T细胞对抗肿瘤抗原，肿瘤的存在 宿主抑制淋巴细胞和抗黑色素瘤T细胞不足诱导的特异性耐受 曲目。目的1将确定CPA对IV期黑色素瘤患者的预治疗 提高DC疫苗接种后的免疫和临床反应。我们将进行L/111随机阶段 接受安慰剂或CPA(500 mg/m2)治疗的IV期黑色素瘤患者的临床试验 用黑色素瘤多肽和KLH冲击的CD34-DC免疫小鼠。作为对照，单独的等量 DC将被HIV多肽作为新抗原冲击，这些新抗原将与负载多肽的DC混合，并 同时给药。主要结果是诱导黑色素瘤特异性CD8+T细胞 豁免权。次要结果是客观的临床反应率。第三阶段的结果是： 减少调节/抑制CD4+T细胞(AIM 2)和启动HIV特异性CD8+T细胞(AIM 3)。