Ruzzi Francesca, Palladini Arianna, Clemmensen Stine, Strøbæk Anette, Buijs Nicolaas, Domeyer Tanja, Dorosz Jerzy, Soroka Vladislav, Grzadziela Dagmara, Rasmussen Christina Jo, Nielsen Ida Busch, Soegaard Max, Semprini Maria Sofia, Scalambra Laura, Angelicola Stefania, Landuzzi Lorena, Lollini Pier-Luigi, Thorn Mette
Alma Mater Institute on Healthy Planet and Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy.
Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy.
Biomedicines. 2022 Oct 20;10(10):2654. doi: 10.3390/biomedicines10102654.
Vaccines are a promising therapeutic alternative to monoclonal antibodies against HER-2+ breast cancer. We present the preclinical activity of an ES2B-C001, a VLP-based vaccine being developed for human breast cancer therapy. FVB mice challenged with HER-2+ mammary carcinoma cells QD developed progressive tumors, whereas all mice vaccinated with ES2B-C001+Montanide ISA 51, and 70% of mice vaccinated without adjuvant, remained tumor-free. ES2B-C001 completely inhibited lung metastases in mice challenged intravenously. HER-2 transgenic Delta16 mice developed mammary carcinomas by 4−8 months of age; two administrations of ES2B-C001+Montanide prevented tumor onset for >1 year. Young Delta16 mice challenged intravenously with QD cells developed a mean of 68 lung nodules in 13 weeks, whereas all mice vaccinated with ES2B-C001+Montanide, and 73% of mice vaccinated without adjuvant, remained metastasis-free. ES2B-C001 in adjuvant elicited strong anti-HER-2 antibody responses comprising all Ig isotypes; titers ranging from 1−10 mg/mL persisted for many months. Antibodies inhibited the 3D growth of human HER-2+ trastuzumab-sensitive and -resistant breast cancer cells. Vaccination did not induce cytokine storms; however, it increased the ELISpot frequency of IFN-γ secreting HER-2-specific splenocytes. ES2B-C001 is a promising candidate vaccine for the therapy of tumors expressing HER-2. Preclinical results warrant further development towards human clinical studies.
疫苗是针对HER-2阳性乳腺癌的单克隆抗体的一种有前景的治疗替代方案。我们展示了ES2B-C001的临床前活性，这是一种正在开发用于人类乳腺癌治疗的基于病毒样颗粒的疫苗。用HER-2阳性乳腺癌细胞QD攻击的FVB小鼠发生了进行性肿瘤，而所有接种ES2B-C001+Montanide ISA 51的小鼠以及70%未使用佐剂接种的小鼠均无肿瘤。ES2B-C001完全抑制了静脉内攻击小鼠的肺转移。HER-2转基因Delta16小鼠在4至8个月大时发生乳腺癌；两次给予ES2B-C001+Montanide可预防肿瘤发生超过1年。用QD细胞静脉内攻击的年轻Delta16小鼠在13周内平均出现68个肺结节，而所有接种ES2B-C001+Montanide的小鼠以及73%未使用佐剂接种的小鼠均无转移。佐剂中的ES2B-C001引发了强烈的抗HER-2抗体反应，包括所有Ig同种型；1至10 mg/mL的滴度持续了数月。抗体抑制了人HER-2阳性曲妥珠单抗敏感和耐药乳腺癌细胞的三维生长。疫苗接种未诱导细胞因子风暴；然而，它增加了分泌IFN-γ的HER-2特异性脾细胞的ELISpot频率。ES2B-C001是治疗表达HER-2的肿瘤的一种有前景的候选疫苗。临床前结果值得进一步开展人体临床研究。
