治疗性癌症疫苗重组表皮生长因子(EGF)-CRM197是以CRM197作为载体蛋白的新型组合结合EGF。用EGF-CRM197疫苗免疫可以诱导高水平的中和抗EGF抗体,其抑制EGF/EGFR信号传导,从而抑制依赖于该信号传导途径的肿瘤的生长。在这里,我们在I期临床试验中描述了重组EGF-CRM197疫苗在晚期实体瘤患者中引起的体液免疫反应,并评估了安全性,耐受性,和该疫苗的免疫原性(CTR20190473)。
■本研究共纳入16名受试者。在6+3设计下,每个给药队列中的患者以0.4mg的剂量皮下给药,0.8mg,和1.6毫克,分别。患者接受免疫诱导疫苗接种(每周一次,连续4周)和加强疫苗接种(每4周一次)。免疫诱导后1周进行安全性评价。给予加强疫苗接种,直到疾病进展发生,不容忍,患者撤回知情同意书,或两次加强疫苗接种后抗EGF测试的阴性结果。
■在晚期实体瘤患者中,EGF-CRM197疫苗接种是安全且耐受性良好的。注射部位的不良反应是受者最常见的不良事件(AE)。在本研究中没有观察到疫苗接种后的严重不良反应。接种疫苗的患者产生了由EGF-CRM197触发的强大的中和抗体反应,从而显着降低了血清中EGF的水平。对于对EGF-CRM197具有超良好抗体反应(sgAR)的肺癌患者,中位无进展生存期(PFS)为4.83个月,显著长于中位PFS为2.10个月的良好抗体应答者(GAR)肺癌患者(P=0.0018)。GAR肺癌患者的中位总生存期(OS)为10.67个月,而sGAR肺癌患者的OS)直到进行分析才达到。sGAR肺癌患者的中位随访时间为14.6个月。
■我们的研究表明,重组EGF-CRM197治疗性癌症疫苗可以在晚期实体瘤患者中诱导良好的免疫反应,并且安全性和耐受性良好,这确保了疫苗的进一步临床开发,以延长EGF-CRM197敏感的晚期实体瘤患者的生存时间。
■http://www.chinadrugtrials.org.cn,标识符CTR20190473、EGF-CRM197。
UNASSIGNED: The therapeutic cancer vaccine recombinant Epidermal Growth Factor (EGF)-CRM197 is a novel combined conjugate EGF with CRM197 as a carrier protein. Immunization with the EGF-CRM197 vaccine can induce high levels of neutralizing anti-EGF antibodies that inhibit EGF/EGFR signaling and thereby suppress growth of tumors that rely on this signaling pathway. Herein, we characterize the humoral immune responses elicited by the recombinant EGF-CRM197 vaccine in patients with advanced solid tumors in a phase I clinical
trial and assess the safety, tolerability, and immunogenicity of this vaccine (CTR20190473).
UNASSIGNED: A total of 16 subjects were enrolled in this
study. Under 6 + 3 design, patients in each dosing cohort were administrated subcutaneously at a dosage of 0.4 mg, 0.8 mg, and 1.6 mg, respectively. The patients received vaccinations for immune induction (once a week for 4 consecutive weeks) and booster vaccinations (once every 4 weeks). Safety evaluation was performed 1 week after the immune induction. Booster vaccination was given until the occurrence of disease progression, intolerance, withdrawal of informed consent by the patient, or negative result of anti-EGF test after two booster vaccinations.
UNASSIGNED: Vaccination with EGF-CRM197 is safe and well-tolerated in patients with advanced solid tumors. Adverse reactions at the injection site were the most common adverse events (AEs) in recipients. No severe adverse reactions post vaccination were observed in the present
study. Vaccinated patients developed a robust neutralizing antibody response triggered by EGF-CRM197 that significantly reduced the levels of EGF in serum. For lung cancer patients who were super good antibody responders (sGAR) to EGF-CRM197, the median progress-free survival (PFS) was 4.83 months, significantly longer than that of the good antibody responder (GAR) patients with lung cancer whose median PFS was 2.10 months (P=0.0018). The median overall survival (OS) of GAR lung cancer patients was 10.67 months while the OS) for sGAR lung cancer patients was not reached until analysis was performed. The median follow-up of the sGAR lung cancer patients was 14.6 months.
UNASSIGNED: Our
study demonstrates that the recombinant EGF-CRM197 therapeutic cancer vaccine can induce a good immune response in patients with advanced solid tumors and is safe and well tolerated, which ensures further clinical development of the vaccine for extending the survival time of EGF-CRM197 sensitive patients with advanced solid tumors.
UNASSIGNED: http://www.chinadrugtrials.org.cn, identifier CTR20190473, EGF-CRM197.