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

描述（由申请人提供）：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，复发是常见的，治愈的可能性可能不超过10%。骨髓瘤患者自体移植后，早期过继转移体内疫苗诱导和体外共刺激的自体t细胞，然后加强免疫，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。当前项目背后的假设是，使用推定的肿瘤疫苗和注射疫苗引发的体外共刺激t细胞的联合免疫治疗可能在移植后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，含有来自hTERT（人类端粒酶的催化亚基）和survivin（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。长期目标是开发一种策略，在自体移植后诱导临床有意义的抗骨髓瘤免疫反应，可以延迟或预防复发。目的1：开展一项试验，在骨髓瘤自体移植的HLA A2阳性患者接受含有HLA A2限制性肽的多肽疫苗，这些多肽疫苗来自hTERT和survivin以及疫苗引发的离体共刺激T细胞，并与HLA A2阴性患者接受共刺激T细胞和肺炎球菌结合物（PCV）对照疫苗（PCV）的队列进行比较，评估这种联合方法的安全性。目的2：在HLA A2+患者队列中，检测对hTERT多肽疫苗的细胞免疫反应的发展，这些患者接受多肽疫苗和疫苗引发和共刺激的t细胞的组合。

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.