Park Mi-Young, Kim Chang-Hyun, Sohn Hyun-Jung, Oh Seong-Taek, Kim Sung-Guh, Kim Tai-Gyu
Department of Microbiology and Immunology, Catholic University of Korea, 505 Banpo-Dong, Seocho-Gu, Seoul 137-701, South Korea.
Vaccine. 2007 Oct 16;25(42):7322-30. doi: 10.1016/j.vaccine.2007.08.037. Epub 2007 Sep 6.
The gradual induction of immune responses by dendritic cell (DC) vaccination or the rapid decrease of adoptively transferred T cells may be major limitations in complete treatment of established tumors by active or passive immunization. The numbers of carcinoembryonic antigen (CEA)-specific T cells increased on 7th day and decreased from 2 weeks after repeated vaccination with CEA-peptide-pulsed DCs. Adoptively transferred CEA-specific T cells were detectable on day 1 and reached their peak by day 4, and thereafter decreased. On the basis of these results, a combined immunotherapy of DC vaccination following adoptive T cell transfer was performed to overcome these limitations of each modality. The injection of DCs within 1 day after adoptive T cell transfer showed a synergistic effect. However, when the DC vaccine was administered on day 3 or 7, CEA-specific T cells gradually declined. This concomitant immunization significantly inhibited the tumor growth than the DC vaccine administered on day 3 or 7 in 10 days tumor model. Moreover, the concomitant immunization showed potent anti-tumor effects resulting in complete inhibition of tumor growth in 2 days tumor model. These results suggest that the optimal interval for the DC vaccination following adoptive T cell transfer is important for boosting antigen-specific T cell responses and this combined immunotherapy may provide a potent therapeutic strategy for cancer treatment.
树突状细胞(DC)疫苗接种诱导免疫反应的渐进性或过继转移T细胞的快速减少,可能是主动或被动免疫完全治疗已建立肿瘤的主要限制因素。用癌胚抗原(CEA)肽脉冲DC重复接种后,CEA特异性T细胞数量在第7天增加,并在2周后减少。过继转移的CEA特异性T细胞在第1天可检测到,并在第4天达到峰值,此后减少。基于这些结果,进行了过继T细胞转移后DC疫苗接种的联合免疫治疗,以克服每种方式的这些局限性。过继T细胞转移后1天内注射DC显示出协同效应。然而,当在第3天或第7天给予DC疫苗时,CEA特异性T细胞逐渐减少。在10天肿瘤模型中,这种联合免疫接种比在第3天或第7天给予DC疫苗更能显著抑制肿瘤生长。此外,在2天肿瘤模型中,联合免疫接种显示出强大的抗肿瘤作用,导致肿瘤生长完全受到抑制。这些结果表明,过继T细胞转移后DC疫苗接种的最佳间隔对于增强抗原特异性T细胞反应很重要,这种联合免疫治疗可能为癌症治疗提供一种有效的治疗策略。