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

ASCT 后使用 hTERT 疫苗进行免疫治疗 疫苗引发的 T 细胞

• 批准号: 7485595
• 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 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7485595
• 关键词: Adoptive Transfer; Apoptotic; Autologous; Autologous Stem Cell Transplantation; Autologous Transplantation; B-Lymphocytes; Cancer Vaccines; Catalytic Domain; Cells; Disease remission; Epitopes; HLA-A2 Antigen; High Dose Chemotherapy; Human; Immune response; Immunotherapy; Infusion procedures; Multiple Myeloma; Patients; Peptide Vaccines; Peptides; Proteins; Recovery; Relapse; Safety; Secondary Immunization; T-Lymphocyte; Telomerase; Transplantation; Vaccination; Vaccines; assay development; cohort; in vivo; lomustine/procarbazine/vincristine; 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（由申请人提供）：高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体内疫苗致敏和离体共刺激的自体T细胞的连续转移，随后进行加强免疫接种，增强了T细胞恢复和疫苗特异性T细胞和B细胞应答的恢复。当前项目背后的假设是，使用推定的肿瘤疫苗和疫苗引发的和离体共刺激的T细胞的输注的组合免疫疗法可能在移植后环境中产生抗肿瘤免疫应答。本研究的肿瘤疫苗将是一种含有HLA-A2限制性表位的多肽疫苗，这些表位来自hTERT（人端粒酶的催化亚基）和生存素（抗凋亡蛋白），它们在骨髓瘤细胞中广泛表达。长期目标是开发一种在自体移植后诱导具有临床意义的抗骨髓瘤免疫应答的策略，该策略可以延迟或预防复发。目标1：进行一项试验，其中骨髓瘤自体移植的HLA A2+患者接受含有来自hTERT和生存素的HLA A2限制性肽的多肽疫苗加上疫苗致敏和离体共刺激的T细胞，并评价与仅接受共刺激的T细胞和肺炎球菌结合物（PCV）对照疫苗（PCV）的HLA A2阴性患者队列相比，这种联合方法的安全性。目标2：在接受多肽疫苗和疫苗致敏和共刺激的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应答的发展。