Immunotherapy after ASCT for MM Using hTERT Vaccination + Vaccine-primed 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会超过10%。在骨髓瘤自体移植后早期过继转移体内疫苗启动的和体外共刺激的自体T细胞，然后加强免疫，可以增强T细胞的恢复和疫苗特异性T细胞和B细胞反应的恢复。目前项目背后的假设是，使用假定的肿瘤疫苗和注射疫苗启动的和体外共刺激的T细胞的联合免疫治疗可以在移植后的环境中产生抗肿瘤免疫反应。这项研究的肿瘤疫苗将是一种包含hTERT(人端粒酶催化亚单位)和Survivin(抗凋亡蛋白)的HLA-A2限制性表位的多肽疫苗，hTERT和Survivin在骨髓瘤细胞中广泛表达。长期目标是开发一种策略，在自体移植后的环境中诱导具有临床意义的抗骨髓瘤免疫反应，以延缓或防止复发。具体目的1：进行一项试验，将人类白细胞抗原A2+的骨髓瘤自体移植患者接种含有来自hTERT和Survivin的人类白细胞抗原A2限制性多肽的多肽疫苗，并与只接受共刺激T细胞和肺炎球菌结合(PCV)对照疫苗(PCV)的患者进行比较，评估这种联合方法的安全性。目的：检测人类白细胞抗原A2+(HLAA2+)多肽疫苗与疫苗诱导和共刺激T细胞联合接种后，对hTERT多肽疫苗的细胞免疫应答情况。

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.