KLH PULSED DENDRITIC CELLS IN AUTOLOGOUS PERIPHERAL BLOOD STEM CELL TRANSPLANT

接受自体外周血干细胞移植(PBSCT)的患者功能免疫活性恢复缓慢。例如，在骨髓移植后，对召回抗原的各种免疫反应通常是迟钝的。在移植后的头三个月接种破伤风或白喉类毒素时，不会导致抗原特异性T细胞反应性的发展。在PBSCT后早期，T细胞对新抗原如KLH的免疫反应很可能在迟发型超敏反应中也有缺陷。虽然免疫缺陷的确切机制尚不清楚，但它们可能存在于参与抗原处理和提呈的树突状细胞水平的免疫反应的传入臂内。成人患者外周血树突状细胞培养的建立增加了将这些细胞用作免疫治疗剂的可能性，以避免传入臂中的这种免疫缺陷，并提供了一种靶向和加速免疫重建的方法。这项研究将比较患者从自体PBSCT中恢复后对新抗原KLH免疫的能力。免疫接种将通过两种方法进行。一组8名患者将接受一系列三次皮内注射新抗原KLH的免疫。我们预测对这种抗原的免疫反应会很低，将在最后一次免疫后2-4周进行评估。这些患者也将接受免疫接种，并作为第一批患者进行评估。这项研究将比较这两组患者的免疫反应，并调查是否可以通过用KLH冲击的树突状细胞免疫患者来克服对KLH缺乏或减弱的免疫反应。

Patients undergoing autologous Peripheral Blood Stem Cell Transplants (PBSCT) have a slow recovery of their functional immunologic activity. As an example, various immunologic responses to recall antigens are usually blunted after bone marrow transplant. Immunization with tetanus or diptheria toxiods does not result in the development of antigen specific T-cell responsiveness when administered during the first three months after transplant. It is likely that the T-cell immune response to a neoantigen such as KLH when measured by the delayed hypersensitivity response may also be defective in the early post-PBSCT stage. While the precise mechanisms of the immune defects are not known, they may reside within the afferent arm of the immune response at the level of the dendritic cell which is involved in antigen processing and presentation. The establishment of dendritic cell cultures from the peripheral blood of adult patients has raised the possibility of now using these cells as an immunotherapeutic agent to circumvent such immune defects in the afferent arm and provide a method to target and accelerate immune reconstitution. This study will compare the ability to immunize patients to the neoantigen KLH after recovery from an autologous PBSCT. Immunizations will be carried out by two methods. A group of 8 patients will be immunized with a series of three intradermal injections of the neoantigen KLH. The immune response to this antigen, which we predict will be low, will be assessed 2-4 weeks after the last immunization. These patients will also be immunized and assessed as the first group of patients. This study will compare the immune response in these two groups of patients and investigate whether an absent or attenuated immune response to KLH may be overcome by immunizing patients with dendritic cells pulsed with KLH.