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在过继性T细胞转移后进行树突状细胞疫苗接种的最佳间隔时间对于增强有效的抗肿瘤免疫力至关重要。

The optimal interval for dendritic cell vaccination following adoptive T cell transfer is important for boosting potent anti-tumor immunity.

作者信息

Park Mi-Young, Kim Chang-Hyun, Sohn Hyun-Jung, Oh Seong-Taek, Kim Sung-Guh, Kim Tai-Gyu

机构信息

Department of Microbiology and Immunology, Catholic University of Korea, 505 Banpo-Dong, Seocho-Gu, Seoul 137-701, South Korea.

出版信息

Vaccine. 2007 Oct 16;25(42):7322-30. doi: 10.1016/j.vaccine.2007.08.037. Epub 2007 Sep 6.

Abstract

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.

摘要

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。

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