Increased vaccine-specific T cell frequency after peptide-based vaccination correlates with increased susceptibility to in vitro stimulation but does not lead to tumor regression.
Increased vaccine-specific T cell frequency after peptide-based vaccination correlates with increased susceptibility to in vitro stimulation but does not lead to tumor regression.
复制标题
DOI：
10.4049/jimmunol.163.11.6292
复制
发表时间：
1999-12
影响因子：
4.4
通讯作者：
Kang-Hun Lee;Ena Wang;M. Nielsen;John R. Wunderlich;S. Migueles;M. Connors;Seth M. Steinberg;Steven A. Rosenberg;F. M. Marincola
中科院分区：
文献类型：
--
作者：
Kang-Hun Lee;Ena Wang;M. Nielsen;John R. Wunderlich;S. Migueles;M. Connors;Seth M. Steinberg;Steven A. Rosenberg;F. M. Marincola
尽管体外致敏试验显示，用MA肽接种后，黑素瘤Ag（MA）特异性CTL反应性增加，但临床反应并不常见。这一悖论质疑从T细胞的体外刺激和扩增中获得的数据是否会导致高估对疫苗的免疫应答。使用HLA/肽四聚体（tHLA），我们直接在23例接种gp 100：209-217（210 M）（g209- 2 M）肽的黑色素瘤患者的PBMC中计数MA特异性T细胞前体频率（TCPF）。7/7例仅用肽治疗的患者和4/5例用肽加IL-12治疗的患者的疫苗特异性TCPF在接种后PBMC中较高（接种后TCPF的范围分别为0.2-2.4%和0.2- 2.5%）。TCPF的增加与对相关表位的体外刺激的敏感性增强相关。奇怪的是，在大多数同时接受IL-2治疗的患者中未观察到接种后TCPF增加（11例患者中的1例;接种后TCPF范围为0.02-1.0%），这与肿瘤消退率增加相关。在这些患者中观察到的TCPF缺乏增加对应于不能引起培养物中疫苗特异性T细胞的扩增。这项研究表明，基于肽的疫苗可以有效地在癌症患者的PBMC中产生可定量的T细胞特异性免疫应答，尽管这种应答与转移性黑色素瘤的临床明显消退无关。
Although in vitro sensitization assays have shown increased melanoma Ag (MA)-specific CTL reactivity after vaccination with MA peptides, clinical responses have been uncommon. This paradox questions whether data obtained from the in vitro stimulation and expansion of T cells lead to an overestimation of the immune response to vaccines. Using HLA/peptide tetramer (tHLA), we enumerated MA-specific T cell precursor frequency (TCPF) directly in PBMC from 23 melanoma patients vaccinated with gp100:209-217(210M) (g209-2M) peptide. Vaccine-specific TCPF was higher in postvaccination PBMC from seven of seven patients treated with peptide alone and four of five patients treated with peptide plus IL-12 (range of postvaccination TCPF, 0.2-2.4% and 0.2-2.5%, respectively). The increased TCPF correlated with enhanced susceptibility to in vitro stimulation with the relevant epitope. Paradoxically, no increase in postvaccination TCPF was observed in most patients who had been concomitantly treated with IL-2 (1 of 11 patients; range of postvaccination TCPF, 0.02-1.0%), a combination associated with enhanced rates of tumor regression. The lack of increase in TCPF seen in these patients corresponded to inability to elicit expansion of vaccine-specific T cells in culture. This study shows that a peptide-based vaccine can effectively generate a quantifiable T cell-specific immune response in the PBMC of cancer patients, though such a response does not associate with a clinically evident regression of metastatic melanoma.