Dendritic cell-based vaccination in metastatic melanoma patients: phase II clinical trial.
Dendritic cell-based vaccination in metastatic melanoma patients: phase II clinical trial.
复制标题
DOI：
10.3892/or.2012.1956
复制
发表时间：
2012-10
期刊：
影响因子：
4.2
通讯作者：
Akiyama Y
中科院分区：
文献类型：
--
作者：
Oshita C;Takikawa M;Kume A;Miyata H;Ashizawa T;Iizuka A;Kiyohara Y;Yoshikawa S;Tanosaki R;Yamazaki N;Yamamoto A;Takesako K;Yamaguchi K;Akiyama Y
转移性和耐药性黑色素瘤可以是免疫治疗的良好靶点，因为它是一种预后非常差的难治性癌症。此前，我们测试了一种基于树突状细胞（DC）的I期疫苗，并证实它是安全的。在本研究中，我们进行了DC疫苗用于转移性黑色素瘤患者的II期试验，主要是HLA-A24基因型，并研究了疫苗的疗效。24例转移性黑色素瘤患者入组了一项基于DC的免疫治疗的II期研究。其中HLA-A24阳性（A*2402）19例，HLA-A2阳性（A*0201）3例。DC生产的方案与I期试验中的方案相似。简而言之，将限制于HLA-A2或A24和KLH的5种黑素瘤相关合成肽（gp 100、酪氨酸酶、MAGE-A2、MAGE-A3和MART-1或MAGE-A1）的混合物用于DC脉冲。最后，将DC皮下（s.c.）在1-5×107/次的剂量范围内注射到腹股沟区。免疫组DC的比例（lin-HLA-DR+）为38.1±13.3%，CD 83 + DC的比例为25.7± 20.8%。关于DC处理的其他参数与阶段I没有不同。免疫应答相关参数包括ELISPOT测定、对肽或KLH的DTH反应、DC注射次数与良好预后相关。ELISPOT反应在75%接种疫苗的患者中呈阳性。接种前抗黑色素瘤抗原抗体滴度的增加也被证明是一个预后因素，但接种后不是。免疫组化结果显示，CD 8、IL-17与预后无关。未观察到超过III级的不良反应。总生存分析显示，DC给予黑色素瘤患者的生存期延长效果显着。这些结果表明，肽混合物处理的DC疫苗可能是一种安全有效的治疗转移性黑色素瘤的延长总生存时间。
Metastatic and chemoresistant melanoma can be a good target of immunotherapy because it is an intractable cancer with a very poor prognosis. Previously, we tested a dendritic cell (DC)-based phase I vaccine, and confirmed that it was safe. In the present study, we performed a phase II trial of a DC vaccine for metastatic melanoma patients with mainly the HLA-A24 genotype, and investigated the efficacy of the vaccine. Twenty-four patients with metastatic melanoma were enrolled into a phase II study of DC-based immunotherapy. The group included 19 HLA-A24-positive (A*2402) patients and 3 HLA-A2-positive (A*0201) patients. The protocol for DC production was similar to that in the phase I trial. Briefly, a cocktail of 5 melanoma-associated synthetic peptides (gp100, tyrosinase, MAGE-A2, MAGE-A3 and MART-1 or MAGE-A1) restricted to HLA-A2 or A24 and KLH were used for DC pulsing. Finally, DCs were injected subcutaneously (s.c.) into the inguinal region in the dose range of 1–5×107 per shot. The DC ratio (lin-HLA-DR+) of the vaccine was 38.1±13.3% and the frequency of CD83+ DCs was 25.7±20.8%. Other parameters regarding DC processing were not different from phase I. Immune response-related parameters including the ELISPOT assay, DTH reaction to peptide or KLH, DC injection numbers were shown to be related to a good prognosis. The ELISPOT reaction was positive in 75% of the patients vaccinated. The increase of anti-melanoma antigen antibody titer before vaccination was also shown to be a prognosis factor, but that post-vaccination was not. Based on immunohistochemical analysis, CD8 and IL-17 were not involved in the prognosis. Adverse effects of more than grade III were not seen. Overall survival analysis revealed a significant survival prolongation effect in DC-given melanoma patients. These results suggest that peptide cocktail-treated DC vaccines may be a safe and effective therapy against metastatic melanoma in terms of prolongation of overall survival time.
登录
查看更多内容
DOI：
10.1084/jem.190.11.1669
发表时间：
1999-12-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Thurner B;Haendle I;Röder C;Dieckmann D;Keikavoussi P;Jonuleit H;Bender A;Maczek C;Schreiner D;von den Driesch P;Bröcker EB;Steinman RM;Enk A;Kämpgen E;Schuler G
通讯作者：
Schuler G
影响因子：
4.4
作者：
Iizuka, Akira;Komiyama, Masaru;Akiyama, Yasuto
通讯作者：
Akiyama, Yasuto
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
影响因子：
3.3
作者：
Desmetz, C.;Cortijo, C.;Solassol, J.
通讯作者：
Solassol, J.
影响因子：
82.9
作者：
MAYORDOMO, JI;ZORINA, T;LOTZE, MT
通讯作者：
LOTZE, MT