Phase I trial of adjuvant mature autologous dendritic cell/allogeneic tumor lysate vaccines in combination with temozolomide in newly diagnosed glioblastoma

替莫唑胺 医学 白细胞清除术 佐剂 疫苗疗法 内科学 肿瘤科 免疫疗法 临床试验 接种疫苗 CD8型 抗原 免疫系统 放射治疗 临床研究阶段 免疫学 癌症 干细胞 生物 川地34 遗传学
作者
Ian F. Parney,S. Keith Anderson,Michael P. Gustafson,Susan Steinmetz,Timothy E. Peterson,Trynda N. Kroneman,Aditya Raghunathan,Brian Patrick O’Neill,Jan C. Buckner,Mary L. Solseth,Allan B. Dietz
出处
期刊:Neuro-oncology advances [Oxford University Press]
卷期号:4 (1) 被引量:6
标识
DOI:10.1093/noajnl/vdac089
摘要

Abstract Background Glioblastoma (GBM) has poor prognosis despite aggressive treatment. Dendritic cell (DC) vaccines are promising, but widespread clinical use has not been achieved, possibly reflecting manufacturing issues of antigen choice and DC potency. We previously optimized vaccine manufacture utilizing allogeneic human GBM tumor cell lysate and potent, mature autologous DCs. Here, we report a phase I study using this optimized DC vaccine in combination with standard therapy. Methods Following surgical resection and radiation with concurrent temozolomide (TMZ), newly diagnosed adult GBM patients received intradermal DC vaccines plus TMZ. Primary endpoints were safety and feasibility. Immune and treatment responses were recorded. Results Twenty-one patients were enrolled in this study. One progressed between leukapheresis and vaccine manufacture. Twenty patients received treatment per protocol. Vaccine doses (≥15) were generated following a single leukapheresis for each patient. No dose-limiting vaccine toxicities were encountered. One patient had symptomatic, histologically proven pseudoprogression. Median progression-free survival was 9.7 months. Median overall survival was 19 months. Overall survival was 25% at 2 years and 10% at 4 years. One patient remains progression-free 5 years after enrollment. Specific CD8 T-cell responses for the tumor-associated antigen gp100 were seen post-vaccination. Patients entered the trial with a leukocyte deficit compared to healthy donors which partly normalized over the course of therapy. Conclusions This vaccine platform is safe and highly feasible in combination with standard therapy for newly diagnosed patients. Imaging, histological, survival, and immunological data suggest a positive biological response to therapy that warrants further investigation.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
花花完成签到 ,获得积分10
1秒前
dasheenly完成签到,获得积分10
1秒前
Owen应助科研通管家采纳,获得10
2秒前
元谷雪应助科研通管家采纳,获得10
2秒前
2秒前
思源应助科研通管家采纳,获得10
2秒前
3秒前
上官若男应助科研通管家采纳,获得10
3秒前
3秒前
llllll发布了新的文献求助10
3秒前
Aaronlucy发布了新的文献求助10
3秒前
oasissmz完成签到,获得积分10
4秒前
4秒前
跳跃尔琴发布了新的文献求助10
5秒前
Jasper应助goodfish采纳,获得10
5秒前
迅哥发布了新的文献求助10
5秒前
丝竹丛中墨未干完成签到,获得积分10
6秒前
supermaltose发布了新的文献求助30
7秒前
su园长应助Ava采纳,获得10
9秒前
科研通AI2S应助超级的煎饼采纳,获得10
10秒前
兜兜应助暴躁的信封采纳,获得10
12秒前
写小人物的大作家完成签到,获得积分10
12秒前
木子李完成签到,获得积分20
12秒前
15秒前
洛洛完成签到,获得积分10
17秒前
安东路完成签到,获得积分10
17秒前
华仔应助白玉汤顿首采纳,获得10
19秒前
19秒前
阿睿发布了新的文献求助10
19秒前
20秒前
20秒前
呼延子默完成签到,获得积分10
21秒前
23秒前
李健应助NANA西采纳,获得10
23秒前
CipherSage应助科研靓仔采纳,获得10
23秒前
神揽星辰入梦完成签到,获得积分10
23秒前
半夏完成签到,获得积分10
23秒前
茹茵湖发布了新的文献求助20
24秒前
24秒前
共享精神应助prince8891采纳,获得10
24秒前
高分求助中
Sustainability in Tides Chemistry 2800
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
юрские динозавры восточного забайкалья 800
English Wealden Fossils 700
Foreign Policy of the French Second Empire: A Bibliography 500
Chen Hansheng: China’s Last Romantic Revolutionary 500
XAFS for Everyone 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3143628
求助须知:如何正确求助?哪些是违规求助? 2795064
关于积分的说明 7813166
捐赠科研通 2451128
什么是DOI,文献DOI怎么找? 1304317
科研通“疑难数据库(出版商)”最低求助积分说明 627213
版权声明 601393