Osterborg A, Werner A, Halapi E, Lundin J, Harmenberg U, Wigzell H, Mellstedt H
Department of Oncology (Radiumhemmet) and Immunological Research Laboratory, Karolinska Hospital, Stockholm, Sweden.
Eur J Haematol. 1997 Jan;58(1):5-13. doi: 10.1111/j.1600-0609.1997.tb01403.x.
Five patients with non-Hodgkin's lymphoma (NHL) and 4 patients with chronic lymphocytic leukaemia (CLL) were treated with the CDR-grafted (rat x human) monoclonal antibody (mAb) Campath-1H (anti-CD52). Tumour regression was noted preferentially in peripheral blood and in the bone marrow but lymph nodes were less affected. Normal blood B and T cells were profoundly reduced in all patients whereas CD16+ NK cells and CD14+ monocytes decreased marginally. In all responding CLL patients CD52-negative T but not B cells appeared during treatment and persisted for several months (4-19+) during unmaintained follow-up. Clonal T cells defined as a predominance of a single T cell receptor (TCR) V gene usage, in one case verified by TCR CDR3 fragment analysis and nucleotide sequencing, emerged within the CD52-/CD8+ cell population during Campath-1H therapy in 2 CLL patients, both achieving a long-lasting remission. The increase in CD8+ T cell expansions (up to 23-fold) during unmaintained remission and follow-up suggest that the clonal CD8+ cells may represent regulatory T cells controlling the growth of the tumour B cell clone. Clonal T cells might thus be a target for an immune therapeutic intervention in B cell tumours.
5例非霍奇金淋巴瘤（NHL）患者和4例慢性淋巴细胞白血病（CLL）患者接受了CDR移植（大鼠×人）单克隆抗体（mAb）Campath-1H（抗CD52）治疗。在外周血和骨髓中优先观察到肿瘤消退，但淋巴结受影响较小。所有患者的正常血液B细胞和T细胞均显著减少，而CD16 + NK细胞和CD14 +单核细胞略有减少。在所有有反应的CLL患者中，治疗期间出现CD52阴性T细胞而非B细胞，并在未维持治疗的随访期间持续数月（4 - 19 +）。在2例CLL患者接受Campath-1H治疗期间，CD52 - / CD8 +细胞群中出现了以单一T细胞受体（TCR）V基因使用为主的克隆性T细胞，1例经TCR CDR3片段分析和核苷酸测序证实，这2例患者均实现了长期缓解。在未维持缓解期和随访期间CD8 + T细胞扩增增加（高达23倍），提示克隆性CD8 +细胞可能代表控制肿瘤B细胞克隆生长的调节性T细胞。因此，克隆性T细胞可能是B细胞肿瘤免疫治疗干预的靶点。
