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
• 负责人: JOSEPH Wayne FAY
• 金额: $ 19.67万
• 依托单位: BAYLOR RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7460927
• 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).

HLA-A*201患者的疫苗接种源自CD34+的树突状细胞（DC）患者 造血细胞祖细胞（CD34+HPC），含有黑色素瘤肽抗原，KLH和流感 肽导致CD8+ T细胞对黑色素瘤肽的免疫和一些临床益处。 通过在黑色素瘤肽存在和 从血液中获得的CD8+ T细胞控制抗原。 T细胞免疫与早期临床结果相关 和生存。早期进展的患者没有T细胞免疫或瞬时T细胞对DC的免疫力 疫苗接种。可能有几种原因是在这些中缺乏DC诱导的CD8+ T细胞免疫力 患者包括：DC无法针对肿瘤抗原的质子T细胞，肿瘤的存在 宿主抑制淋巴细胞诱导的特异性耐受性，抗黑素瘤T细胞不足 曲目。 AIM 1将确定是否患有CPA的IV期黑色素瘤患者的治疗是否 DC疫苗接种后改善免疫和临床反应。我们将执行一个随机的L/LL相位 随后将接受安慰剂或CPA（500mg/m2）的IV期黑色素瘤患者的临床试验 通过用黑色素瘤肽和KLH脉冲的CD34-DC疫苗接种。作为控制，一个单独的等分试样 DC将用HIV肽作为新抗原脉冲，将其与肽负载的DC混合，并将其混合 同时管理。主要结果是诱导黑色素瘤特异性CD8+T细胞 免疫。次要结果是客观临床反应的速度。第三级结果是： 减少调节/抑制器CD4+T细胞（AIM 2）和HIV特异性CD8+T细胞的启动（AIM 3）。