Immunotherapy after ASCT for MM Using hTERT Vaccination + Vaccine-primed T cells

ASCT 后使用 hTERT 疫苗进行 MM 免疫治疗 疫苗引发的 T 细胞

• 批准号: 7328907
• 负责人: AARON P RAPOPORT
• 金额: $ 28.5万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-14 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7328907
• 关键词: Adoptive Transfer; Allogenic; Animal Model; Antibody Formation; Antigens; Apoptotic; Autologous; Autologous Stem Cell Transplantation; Autologous Transplantation; B-Lymphocytes; Cancer Vaccines; Catalytic Domain; Cells; Clinical; Clinical Trials; Combined Vaccines; Development; Disease; Disease remission; Disease-Free Survival; Donor person; Dose; Enrollment; Epitopes; HLA-A2 Antigen; High Dose Chemotherapy; Human; Immune; Immune Tolerance; Immune response; Immunotherapy; Infusion procedures; Mediating; Minority; Multiple Myeloma; Patients; Peptide Vaccines; Peptides; Phase; Pneumococcal 7-Valent Conjugate Vaccine; Pneumococcal conjugate vaccine; Proteins; Publishing; Rate; Recovery; Relapse; Safety; Secondary Immunization; T-Lymphocyte; Telomerase; Toxic effect; Transplantation; Tumor Antigens; Vaccination; Vaccines; assay development; cohort; graft vs host disease; improved; in vivo; mortality; prevent; response; restoration; survivin; tumor

DESCRIPTION (provided by applicant): High-dose chemotherapy and autologous stem cell transplantation (ASCT) provides myeloma patients with the best opportunity for complete remission and long-term survival. However, relapses are common and the likelihood of cure is probably no better than 10%. Adoptive transfer of in-vivo vaccine-primed and ex-vivo costimulated autologous T-cells early after autotransplantation for myeloma followed by booster immunizations augments T-cell recovery and restoration of vaccine-specific T-cell and B-cell responses. The hypothesis behind the current project is that combination immunotherapy using a putative tumor vaccine and infusions of vaccine-primed and ex-vivo costimulated T-cells may generate anti-tumor immune responses in the post-transplant setting. The tumor vaccine for this study will be a multi-peptide vaccine containing HLA-A2 restricted epitopes from hTERT (catalytic subunit of human telomerase) and survivin (anti-apoptotic protein) - which are widely expressed in myeloma cells. The long-term objective is to develop a strategy for inducing clinically meaningful anti-myeloma immune responses in the post-autotransplant setting which can delay or prevent relapses. Specific Aims AIM 1: To conduct a trial in which HLA A2+ patients who are autografted for myeloma receive a multi-peptide vaccine containing HLA A2 - restricted peptides from hTERT and survivin plus vaccine-primed and ex-vivo costimulated T-cells and to evaluate the safety of this combined approach in comparison to an HLA A2 negative cohort of patients who receive costimulated T- cells and a pneumococcal conjugate (PCV) control vaccine (PCV) only. AIM 2: To assay for development of cellular immune responses to the hTERT multi-peptide vaccine in the cohort of HLA A2+ patients who receive the combination of the multi-peptide vaccine and the vaccine-primed and costimulated T-cells.

描述（申请人提供）：大剂量化疗和自体干细胞移植（ASCT）为骨髓瘤患者提供了完全缓解和长期生存的最佳机会。然而，复发很常见，治愈的可能性可能不超过 10%。骨髓瘤自体移植后早期过继转移体内疫苗引发和体外共刺激的自体 T 细胞，随后进行加强免疫，可增强 T 细胞恢复和疫苗特异性 T 细胞和 B 细胞反应的恢复。当前项目背后的假设是，使用假定的肿瘤疫苗和注射疫苗引发的体外共刺激 T 细胞的联合免疫疗法可能会在移植后环境中产生抗肿瘤免疫反应。本研究的肿瘤疫苗将是一种多肽疫苗，含有 hTERT（人端粒酶催化亚基）和生存素（抗凋亡蛋白）的 HLA-A2 限制性表位，这些表位在骨髓瘤细胞中广泛表达。长期目标是制定一种策略，在自体移植后诱导具有临床意义的抗骨髓瘤免疫反应，从而延迟或预防复发。具体目标 目标 1：进行一项试验，其中因骨髓瘤自体移植的 HLA A2+ 患者接受含有 HLA A2（来自 hTERT 和生存素的限制性肽）以及疫苗引发和离体共刺激 T 细胞的多肽疫苗，并与接受共刺激 T 细胞和体外共刺激 T 细胞的 HLA A2 阴性患者队列相比，评估这种组合方法的安全性。 仅肺炎球菌结合疫苗 (PCV) 对照疫苗 (PCV)。目标 2：在接受多肽疫苗与疫苗引发和共刺激 T 细胞组合的 HLA A2+ 患者队列中，测定对 hTERT 多肽疫苗的细胞免疫反应的发展。