Einsele Hermann, Roosnek Eddy, Rufer Nathalie, Sinzger Christian, Riegler Susanne, Löffler Jürgen, Grigoleit Ulrich, Moris Arnaud, Rammensee Hans-Georg, Kanz Lothar, Kleihauer Annette, Frank Friederike, Jahn Gerhard, Hebart Holger
Medizinische Klinik und Poliklinik, Abteilung II, Tübingen, Germany.
Blood. 2002 Jun 1;99(11):3916-22. doi: 10.1182/blood.v99.11.3916.
We adoptively transferred donor-derived cytomegalovirus (CMV)-specific T-cell lines into 8 stem cell transplant recipients lacking CMV-specific T-cell proliferation. All patients, of whom one was infected by a CMV strain that was genotypically ganciclovir resistant, had received unsuccessful antiviral chemotherapy for more than 4 weeks. CMV-specific lines had been prepared by repetitive stimulation with CMV antigen, which increased the percentage of CMV-specific T cells and ablated alloreactivity completely even against patients mismatched for 1 to 3 HLA antigens. After transfer of 10(7) T cells/m(2) at a median of 120 days (range, 79-479 days) after transplantation, no side effects were noticed. Despite cessation of antiviral chemotherapy, the CMV load dropped significantly in all 7 evaluable patients, with a maximal reduction after a median of 20 days (range, 5-31 days). In 2 patients with high virus load, the antiviral effect was only transient. One of these patients received a second T-cell infusion, which cleared the virus completely. At a median of 11 days after transfer, CMV-specific T-cell proliferation was demonstrated in 6 patients, and an increase in CMV-specific CD4(+) T cells was demonstrated in 5 patients. In 6 patients, 1.12 to 41 CMV-specific CD8(+) T cells/microL blood were detected at a median of 13 days after transfer, with an increase in all patients lacking CMV-specific CD8(+) T cells prior to transfer. Hence, anti-CMV cellular therapy was successful in 5 of 7 patients, whereas in 2 of 7 patients, who received an intensified immune suppression at the time of or after T-cell therapy, only transient reductions in virus load were obtained.
我们将供体来源的巨细胞病毒（CMV）特异性T细胞系过继转移至8例缺乏CMV特异性T细胞增殖的干细胞移植受者体内。所有患者均接受了超过4周的抗病毒化疗但未成功，其中1例感染了基因型耐更昔洛韦的CMV毒株。CMV特异性T细胞系通过用CMV抗原重复刺激制备，这增加了CMV特异性T细胞的百分比，并完全消除了同种异体反应性，即使是针对1至3个HLA抗原不匹配的患者。在移植后中位数120天（范围79 - 479天）输入10⁷个T细胞/m²后，未观察到副作用。尽管停止了抗病毒化疗，但所有7例可评估患者的CMV载量均显著下降，中位数20天（范围5 - 31天）后达到最大降幅。2例病毒载量高的患者，抗病毒效果只是短暂的。其中1例患者接受了第二次T细胞输注，病毒被完全清除。在转移后中位数11天，6例患者出现CMV特异性T细胞增殖，5例患者出现CMV特异性CD4⁺T细胞增加。在6例患者中，转移后中位数13天检测到每微升血液中有1.12至41个CMV特异性CD8⁺T细胞，所有转移前缺乏CMV特异性CD8⁺T细胞的患者数量均增加。因此，抗CMV细胞疗法在7例患者中的5例取得成功，而在T细胞治疗时或治疗后接受强化免疫抑制的7例患者中的2例，仅获得了病毒载量的短暂降低。
