KLH PULSED DENDRITIC CELLS IN AUTOLOGOUS PERIPHERAL BLOOD STEM CELL TRANSPLANT

接受自体外周血干细胞移植（PBSCT）的患者的功能性免疫活性恢复缓慢。 例如，骨髓移植后，对回忆抗原的各种免疫反应通常减弱。 当在移植后的前三个月内接种破伤风或白喉疫苗时，不会导致抗原特异性T细胞应答的发展。 这是可能的，T细胞免疫反应的新抗原，如KLH时，测量迟发型超敏反应也可能是有缺陷的PBSCT后早期阶段。 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加工和呈递的树突细胞水平的免疫应答的传入臂内。 从成年患者外周血中建立树突状细胞培养物提高了现在使用这些细胞作为免疫抑制剂以规避传入臂中的这种免疫缺陷并提供靶向和加速免疫重建的方法的可能性。 本研究将比较患者从自体PBSCT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名患者将用一系列的三次新抗原KLH皮内注射进行免疫。 我们预测对该抗原的免疫应答较低，将在末次免疫后2-4周进行评估。 这些患者也将作为第一组患者进行免疫接种和评估。 本研究将比较这两组患者的免疫应答，并研究是否可以通过用KLH脉冲的树突状细胞免疫患者来克服对KLH的免疫应答缺失或减弱。

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.