Hus I, Schmitt M, Tabarkiewicz J, Radej S, Wojas K, Bojarska-Junak A, Schmitt A, Giannopoulos K, Dmoszyńska A, Roliński J
Department of Hematooncology, Medical University of Lublin, Lublin, Poland.
Leukemia. 2008 May;22(5):1007-17. doi: 10.1038/leu.2008.29. Epub 2008 Mar 6.
Recently, we described that vaccination with allogeneic dendritic cells (DCs) pulsed with tumor cell lysate generated specific CD8+ T cell response in patients with B-cell chronic lymphocytic leukemia (B-CLL). In the present study, the potential of autologous DCs pulsed ex vivo with tumor cell lysates to stimulate antitumor immunity in patients with B-CLL in early stages was evaluated. Twelve patients at clinical stage 0-2 as per Rai were vaccinated intradermally up to eight times with a mean number of 7.4 x 10(6) DCs pulsed with B-CLL cell lysate. We observed a decrease of peripheral blood leukocytes and CD19+/CD5+ leukemic cells in five patients, three patients showed a stable disease and four patients progressed despite DC vaccination. A significant increase of specific cytotoxic CD8+ T lymphocytes against the leukemia-associated antigens RHAMM or fibromodulin was detected in four patients after DC vaccination. In patients with a clinical response, an increase of interleukin 12 (IL-12) serum levels and a decrease of the frequency of CD4+CD25(+)FOXP3+ T regulatory cells were observed. Taken together, the study demonstrated that vaccination with autologous DC in CLL patients is feasible and safe. Immunological and to some extend hematological responses could be noted, justifying further investigation on this immunotherapeutical approach.
最近,我们描述了用肿瘤细胞裂解物脉冲处理的同种异体树突状细胞(DCs)进行疫苗接种,在B细胞慢性淋巴细胞白血病(B-CLL)患者中产生了特异性CD8 + T细胞反应。在本研究中,评估了用肿瘤细胞裂解物在体外脉冲处理的自体DCs刺激早期B-CLL患者抗肿瘤免疫的潜力。根据Rai分期,12例临床0-2期的患者皮内接种高达8次,平均接种7.4×10(6)个用B-CLL细胞裂解物脉冲处理的DCs。我们观察到5例患者外周血白细胞和CD19 + / CD5 +白血病细胞减少,3例患者疾病稳定,4例患者尽管接种了DC疫苗仍病情进展。在4例患者接种DC疫苗后,检测到针对白血病相关抗原RHAMM或纤调蛋白的特异性细胞毒性CD8 + T淋巴细胞显著增加。在有临床反应的患者中,观察到白细胞介素12(IL-12)血清水平升高和CD4 + CD25(+)FOXP3 + T调节细胞频率降低。综上所述,该研究表明在CLL患者中接种自体DC是可行且安全的。可以观察到免疫反应以及在一定程度上的血液学反应,证明对这种免疫治疗方法进行进一步研究是合理的。