Slavin Shimon
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Cell Therapy and Transplantation Research Center, The Danny Cunniff Leukemia Research Laboratory, Hadassah University Hospital, Jerusalem, Israel.
Int J Hematol. 2003 Oct;78(3):195-207. doi: 10.1007/BF02983795.
Allogeneic bone marrow or blood stem cell transplantation represents an important therapeutic tool for the treatment of otherwise incurable cancer and a large spectrum of nonmalignant diseases. Until recently, bone marrow transplantation was used primarily to eliminate malignant, genetically abnormal, or otherwise deficient stem cells; hence, highly toxic myeloablative regimens were considered mandatory for the eradication of undesirable cells of host origin. Recent data suggest that high-dose chemoradiotherapy may be successively replaced by nonmyeloablative stem cell transplantation (NST), which represents a safer biologic tool that involves the induction of host-versus-graft transplantation tolerance. NST thus provides allogeneic donor lymphocytes with the capacity to induce immune-mediated graft-versus-malignancy effects, either against mismatched minor or major histocompatibility alloantigens or against tumor-specific or tumor-associated antigens expressed by tumor or other hematologic cells of host origin. The future goals of the wider and safer clinical application of NST for the treatment of a larger number of indications and larger numbers of patients in need depend, on the one hand, on the development of more effective and safer modalities for maximizing the antitumor potential of donor lymphocytes (T-cells as well as natural killer and natural killer T-cells). On the other hand, these goals depend on using more selective approaches for targeting anticancer effector cells to their target cells. Such changes will thus set the stage for smarter rather than stronger modalities for the treatment of malignant and life-threatening nonmalignant diseases.
异基因骨髓或血液干细胞移植是治疗其他方法无法治愈的癌症以及多种非恶性疾病的重要治疗手段。直到最近，骨髓移植主要用于清除恶性、基因异常或其他缺陷的干细胞；因此，高毒性的清髓方案被认为是根除宿主来源的不良细胞所必需的。最近的数据表明，高剂量放化疗可能会相继被非清髓性干细胞移植（NST）所取代，NST是一种更安全的生物学手段，涉及诱导宿主对移植物的移植耐受。因此，NST为异基因供体淋巴细胞提供了诱导免疫介导的移植物抗恶性肿瘤效应的能力，这种效应可以针对不匹配的次要或主要组织相容性同种异体抗原，也可以针对宿主来源的肿瘤或其他血液细胞表达的肿瘤特异性或肿瘤相关抗原。NST在更广泛、更安全地临床应用以治疗更多适应症和更多有需要的患者方面的未来目标，一方面取决于开发更有效、更安全的方法来最大化供体淋巴细胞（T细胞以及自然杀伤细胞和自然杀伤T细胞）的抗肿瘤潜力。另一方面，这些目标取决于使用更具选择性的方法将抗癌效应细胞靶向到其靶细胞。因此，这些变化将为治疗恶性和危及生命的非恶性疾病奠定更智能而非更强有力的治疗模式基础。
