Ann Surg：肿瘤疫苗可改善结直肠癌患者转移灶切除术后生存结局

在2013年5月7日在线出版的《外科学年鉴》(Annals of Surgery)杂志上，发表了美国杜克大学Michael A. Morse博士等人的一项研究结果，该研究针对可进行手术切除的转移性结直肠癌患者(CRC)，旨在考察基于树突状细胞(DC)及编码CEA(癌胚抗原)与MUC1 (PANVAC)痘病毒载体的一类或两类疫苗是否可以延长患者的生存时间。转移性CRC患者在接受完全切除后常出现复发。针对CRC的免疫应答与较低的复发率有关，这表明作为一种辅助治疗手段，肿瘤疫苗可发挥一定作用。在抗肿瘤抗原方面，DC与痘病毒载体可起到有效的激活作用。

该研究入选对象为接受CRC转移灶切除及围手术期化疗后的无病期患者(n = 74)，患者随机接受经自体DC修饰的PANVAC (DC/PANVAC)注射治疗或PANVAC联合每剂次的GM-CSF(粒细胞-巨噬细胞集落刺激因子)注射治疗。研究终点为无复发生存率、总生存率及CEA特异性免疫应答率。研究人员将患者的临床结局与未经免疫的同期患者组群进行了比较，后者也曾接受过CRC转移灶切除以及类似的围手术期化疗，也就是说，这些患者原本也可作为该研究的合格入选患者。

研究结果表明，两组患者的2年无复发生存率相似(DC/PANVAC与PANVAC/GM-CSF 组分别为47% 与55%) (χ P = 0.48)。经过中位时间为35.7个月的随访后，DC/PANVAC组37例患者中出现2例死亡，PANVAC/GM-CSF组的37例患者中则出现了5例死亡。从统计学角度，两组患者在T细胞对CEA的应答率及应答程度方面类似。与同期未接受免疫的患者群体相比，接受免疫的患者群体可取得较好的生存结局。

研究人员最后认为，DC及痘病毒载体疫苗具有类似活性。同时与同期未接受免疫的患者群体相比，接受免疫的患者群体的生存时间较长，这一结论为一项针对转移灶切除后患者，旨在对比痘病毒载体疫苗接种与常规随访的随机试验(NCT00103142)提供了支持。

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.
Abstract
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).