Talmadge J E
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-5660, USA.
In Vivo. 1994 Nov-Dec;8(5):675-90.
In summary, a number of new immunotherapeutic strategies are being developed to take advantage of the reduced tumor burden that occurs following induction chemotherapy and stem cell transplantation. Novel strategies to accelerate hematopoietic reconstitution have become accepted and/or are rapidly being implemented. These include the use of PBSC's as compared to BM stem cells. PBSC's appear to accelerate hematopoietic reconstitution, have a lower likelihood of occult tumor cell contamination and contain a greater number of T cells in the product which may allow an accelerated immunologic reconstitution post transplantation. Similarly, the concept of GVT is no longer viewed as an epiphenomenon but following allotransplantation is an objectively supported and clinically important phenomena. Further, post transplantation adjunct therapy with a variety of immunoaugmenting agents may induce an autologous GVT response. Additional benefits of PBSCT beyond those associated with the accelerated hematopoietic reconstitution and concomitant tumor reduction is the reduced expense of transplantation due to a shorter stay within the hospital. The isolation of stem cells (CD-34+) with or without ex vivo expansion to reduce the amount of stem cell product required is also an exciting new clinical strategy. This approach may also reduce the tumor cell contamination of the stem cell product, result in a more rapid hematologic reconstitution and reduce costs. However, it also has a potential down side due to a reduced infusion of mature and functional T cells. The comparison of PBSC to BM for transplantation of NHL suggests that the infusion of, or rapid reconstitution of, a functional immune system may have therapeutic benefit as discussed above. Thus, in addition to strategies based on the induction of an autologous GVT there is the need to develop/initiate clinic strategies to overcome the immunosuppression-anergy associated with stem cell transplantation, as well as, augment tumor specific T cell responses to "mop up" the residual tumor cells post transplantation. Clearly the clinical use of cytokines, especially in conjunction with PBSCT, has as a goal not only the reduction of morbidity and mortality associated with standard therapy but also dose intensification and scheduled compression so that increasing numbers of individuals may survive their current neoplasia. However, to date the use of the ex vivo expansion of stem and progenitor cells remains a largely unexplored clinical application for use in transplantation.(ABSTRACT TRUNCATED AT 400 WORDS)
总之，正在研发多种新的免疫治疗策略，以利用诱导化疗和干细胞移植后出现的肿瘤负荷减轻这一情况。加速造血重建的新策略已被接受和/或正在迅速实施。这些策略包括使用外周血干细胞（PBSC）而非骨髓干细胞。外周血干细胞似乎能加速造血重建，隐匿肿瘤细胞污染的可能性较低，且产品中含有更多数量的T细胞，这可能使移植后的免疫重建加速。同样，移植物抗宿主病（GVT）的概念不再被视为一种附带现象，而是在同种异体移植后是一种有客观依据且临床重要的现象。此外，移植后用多种免疫增强剂进行辅助治疗可能诱导自体GVT反应。外周血干细胞移植（PBSCT）除了与加速造血重建及随之而来的肿瘤缩小相关的益处外，还因住院时间缩短而降低了移植费用。分离有或无体外扩增的干细胞（CD - 34 +）以减少所需干细胞产品的量也是一种令人兴奋的新临床策略。这种方法还可能减少干细胞产品中的肿瘤细胞污染，实现更快的血液学重建并降低成本。然而，由于成熟和功能性T细胞的输注减少，它也有潜在的不利方面。将外周血干细胞与骨髓用于非霍奇金淋巴瘤（NHL）移植的比较表明，如上文所讨论的，输注或快速重建功能性免疫系统可能具有治疗益处。因此，除了基于诱导自体GVT的策略外，还需要制定/启动临床策略来克服与干细胞移植相关的免疫抑制 - 无反应状态，以及增强肿瘤特异性T细胞反应以“清除”移植后残留的肿瘤细胞。显然，细胞因子的临床应用，特别是与外周血干细胞移植联合使用时，其目标不仅是降低与标准治疗相关的发病率和死亡率，还包括剂量强化和疗程缩短，以便越来越多的个体能够从当前的肿瘤疾病中存活下来。然而，迄今为止，干细胞和祖细胞的体外扩增在移植中的临床应用在很大程度上仍未得到探索。（摘要截断于400字）
