Conry R M, Khazaeli M B, Saleh M N, Allen K O, Barlow D L, Moore S E, Craig D, Arani R B, Schlom J, LoBuglio A F
Comprehensive Cancer Center, The University of Alabama at Birmingham, 35294-3300, USA.
Clin Cancer Res. 1999 Sep;5(9):2330-7.
The principal objectives of this trial were twofold: (a) to examine the safety and relative efficacy of intradermal needle injection versus s.c. jet administration of a carcinoembryonic antigen (CEA)-encoding recombinant vaccinia virus (rV-CEA) over a limited dose range and (b) to evaluate CEA-specific immune responses or antitumor effects induced by rV-CEA vaccination. Patients were randomly assigned to one of two groups, depending upon the technique of vaccine administration. All 20 patients received two doses of 10(7) or 10(8) pfu of rV-CEA at a 4-week interval. Toxicity was limited to modest local inflammation at the inoculation site as well as low-grade fever and increased fatigue, each affecting fewer than 20% of the patients. No evidence of CEA-specific lymphoproliferation, interleukin 2 release, delayed-type hypersensitivity, or antibody response was observed. Thus, the efficacy comparison between the two administration techniques was based upon the induction of immune responses to the vaccinia virus vector. Both techniques induced vaccinia-specific lymphoproliferation, interleukin 2 release, and antibody responses of comparable magnitude and frequency as well as protected 80% of patients against pustule formation following vaccinia scarification. Thus, there is no compelling reason to recommend one administration technique over the other based upon toxicity or efficacy. We have selected s.c. jet injection for subsequent trials of rV-CEA based on the ability to accommodate larger injection volumes, enhanced standardization between clinicians, and avoidance of needles that could transmit the vaccine or blood-borne pathogens to health care workers. We recommend use of 10(8) pfu doses for subsequent trials of recombinant vaccinia virus vaccines based upon the favorable toxicity profile and more consistent local pustule formation indicative of an adequate inoculation of live virus. No objective clinical responses to the rV-CEA vaccine were observed among this population of patients with widely metastatic adenocarcinoma.
（a）在有限剂量范围内，研究皮内针注射与皮下喷射给予癌胚抗原（CEA）编码重组痘苗病毒（rV-CEA）的安全性和相对疗效；（b）评估rV-CEA疫苗接种诱导的CEA特异性免疫反应或抗肿瘤作用。根据疫苗接种技术，患者被随机分为两组。所有20名患者均接受两剂10⁷或10⁸pfu的rV-CEA，间隔4周。毒性仅限于接种部位的轻度局部炎症以及低热和疲劳加重，每种情况影响不到20%的患者。未观察到CEA特异性淋巴细胞增殖、白细胞介素2释放、迟发型超敏反应或抗体反应的证据。因此，两种给药技术之间的疗效比较基于对痘苗病毒载体免疫反应的诱导。两种技术均诱导了程度和频率相当的痘苗特异性淋巴细胞增殖、白细胞介素2释放和抗体反应，并保护80%的患者在痘苗划痕后不形成脓疱。因此，基于毒性或疗效，没有令人信服的理由推荐一种给药技术优于另一种。基于能够容纳更大注射量、提高临床医生之间的标准化以及避免可能将疫苗或血源性病原体传播给医护人员的针头，我们选择皮下喷射注射用于rV-CEA的后续试验。基于良好的毒性特征和更一致的局部脓疱形成（表明活病毒接种充分），我们建议在重组痘苗病毒疫苗的后续试验中使用10⁸pfu剂量。在这群广泛转移腺癌患者中，未观察到对rV-CEA疫苗的客观临床反应。
