A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer.
A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer.
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DOI：
10.1186/1479-5876-3-9
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发表时间：
2005-02-21
影响因子：
7.4
通讯作者：
Lyerly HK
中科院分区：
文献类型：
--
作者：
Morse MA;Garst J;Osada T;Khan S;Hobeika A;Clay TM;Valente N;Shreeniwas R;Sutton MA;Delcayre A;Hsu DH;Le Pecq JB;Lyerly HK
仍然需要开发更有效的癌症免疫治疗策略。外泌体，表达高水平的窄谱细胞蛋白的细胞衍生的脂质囊泡，代表了用于递送高水平抗原连同共刺激分子的新平台。我们进行了这项研究，以测试负载有法师肿瘤抗原的自体树突状细胞（DC）衍生的外泌体（DEX）在非小细胞肺癌（NSCLC）患者中的安全性、可行性和有效性。这项I期研究入组了肿瘤表达MAGE-A3或A4的经预治疗IIIb期（N = 4）和IV期（N = 9）NSCLC的HLA A2+患者。患者接受白细胞去除术以产生DC，从中产生DEX并负载MAGE-A3、-A4、-A10和法师-3DPO 4肽。患者每周接受4次DEX给药。13例患者入组，9例完成治疗。评价了三种DEX制剂;所有制剂均耐受良好，仅发生与DEX使用相关的1-2级不良事件（注射部位反应（N = 8）、流感样疾病（N = 1）和外周手臂疼痛（N = 1））。从DEX首次给药至疾病进展的时间为30至429+天。3名患者在第一次DEX给药前发生疾病进展。第一次DEX给药后患者的生存期为52-665+天。在3/9例患者中检测到对法师肽的DTH反应性。在患者中检测到如下免疫应答：1/3的MAGE特异性T细胞应答，2/4的NK细胞溶解活性增加。DEX疫苗的生产是可行的，DEX治疗在晚期NSCLC患者中耐受性良好。一些患者经历了疾病的长期稳定和免疫效应物的激活
There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1–2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52–665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors
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影响因子：
82.9
作者：
Zitvogel, L;Regnault, A;Amigorena, S
通讯作者：
Amigorena, S
影响因子：
2.2
作者：
Lamparski, HG;Metha-Damani, A;Le Pecq, JB
通讯作者：
Le Pecq, JB
影响因子：
3.9
作者：
Hsu, DH;Paz, P;Le Pecq, JB
通讯作者：
Le Pecq, JB
影响因子：
5.3
作者：
Gotoh, K;Yatabe, Y;Mitsudomi, T
通讯作者：
Mitsudomi, T
影响因子：
82.9
作者：
Wolfers, J;Lozier, A;Zitvogel, L
通讯作者：
Zitvogel, L