一项关于用编码 CEA 和 MUC1 的痘病毒载体修饰的树突状细胞免疫接种与相同的痘病毒载体加 GM-CSF 治疗切除的转移性结直肠癌的随机 II 期研究。
A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer.
机构信息
Departments of *Medicine, †Biostatistics and Bioinformatics, ‡Surgery, Duke University Medical Center §Duke Comprehensive Cancer Center, ‖Department of Immunology, Duke University Medical Center, Durham, NC ¶Georgetown University, Washington, DC **MD Anderson Cancer Center, Houston, TX ††Wake Forest University Baptist Medical Center, Winston-Salem, NC ‡‡Earle Chiles Cancer Center, Providence Portland Medical Center, Portland, OR §§Medical University of South Carolina, Charleston, SC ‖‖Moffitt Cancer Center, Tampa, FL. Dr Chang is now with Virginia Oncology Associates, Newport News, VA. Dr Clay is now with GlaxoSmithKline, Rixensart, Belgium.
出版信息
Ann Surg. 2013 Dec;258(6):879-86. doi: 10.1097/SLA.0b013e318292919e.
OBJECTIVE
To determine whether 1 of 2 vaccines based on dendritic cells (DCs) and poxvectors encoding CEA (carcinoembryonic antigen) and MUC1 (PANVAC) would lengthen survival in patients with resected metastases of colorectal cancer (CRC).
BACKGROUND
Recurrences after complete resections of metastatic CRC remain frequent. Immune responses to CRC are associated with fewer recurrences, suggesting a role for cancer vaccines as adjuvant therapy. Both DCs and poxvectors are potent stimulators of immune responses against cancer antigens.
METHODS
Patients, disease-free after CRC metastasectomy and perioperative chemotherapy (n = 74), were randomized to injections of autologous DCs modified with PANVAC (DC/PANVAC) or PANVAC with per injection GM-CSF (granulocyte-macrophage colony-stimulating factor). Endpoints were recurrence-free survival overall survival, and rate of CEA-specific immune responses. Clinical outcome was compared with that of an unvaccinated, contemporary group of patients who had undergone CRC metastasectomy, received similar perioperative therapy, and would have otherwise been eligible for the study.
RESULTS
Recurrence-free survival at 2 years was similar (47% and 55% for DC/PANVAC and PANVAC/GM-CSF, respectively) (χ P = 0.48). At a median follow-up of 35.7 months, there were 2 of 37 deaths in the DC/PANVAC arm and 5 of 37 deaths in the PANVAC/GM-CSF arm. The rate and magnitude of T-cell responses against CEA was statistically similar between study arms. As a group, vaccinated patients had superior survival compared with the contemporary unvaccinated group.
CONCLUSIONS
Both DC and poxvector vaccines have similar activity. Survival was longer for vaccinated patients than for a contemporary unvaccinated group, suggesting that a randomized trial of poxvector vaccinations compared with standard follow-up after metastasectomy is warranted. (NCT00103142).
目的
确定基于树突状细胞（DC）和编码癌胚抗原（CEA）和 MUC1（PANVAC）的痘病毒载体的 2 种疫苗中的 1 种是否会延长结直肠癌（CRC）切除转移患者的生存时间。
背景
CRC 完全切除后复发仍然频繁。对 CRC 的免疫反应与较少的复发相关，这表明癌症疫苗作为辅助治疗的作用。树突状细胞和痘病毒载体都是针对癌症抗原的免疫反应的有效刺激物。
方法
患者在 CRC 转移瘤切除术和围手术期化疗后无疾病（n = 74），随机接受自体 DC 修饰的 PANVAC（DC/PANVAC）或每剂 PANVAC 联合 GM-CSF（粒细胞-巨噬细胞集落刺激因子）注射。终点是无复发生存期、总生存期和 CEA 特异性免疫反应率。临床结果与未接种疫苗、接受类似围手术期治疗且符合研究条件的同期 CRC 转移瘤切除术患者进行了比较。
结果
2 年无复发生存率相似（DC/PANVAC 组为 47%，PANVAC/GM-CSF 组为 55%）（χ P = 0.48）。在中位数为 35.7 个月的随访中，DC/PANVAC 组有 2 例死亡，而 PANVAC/GM-CSF 组有 5 例死亡。研究组之间针对 CEA 的 T 细胞反应的速率和幅度统计学上相似。作为一个群体，接种疫苗的患者比同期未接种疫苗的患者具有更好的生存。
结论
两种 DC 和痘病毒载体疫苗均具有相似的活性。接种疫苗的患者的生存时间长于同期未接种疫苗的患者，这表明需要进行痘病毒疫苗接种与转移瘤切除后标准随访的随机试验。（NCT00103142）。
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