التفاصيل البيبلوغرافية
| العنوان: |
Prevention and Therapy of Metastatic HER-2 + Mammary Carcinoma with a Human Candidate HER-2 Virus-like Particle Vaccine. |
| المؤلفون: |
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 |
| المصدر: |
Biomedicines; Oct2022, Vol. 10 Issue 10, pN.PAG-N.PAG, 17p |
| مصطلحات موضوعية: |
VIRUS-like particles, CANCER cell growth, TRANSGENIC mice, CYTOKINE release syndrome, MONOCLONAL antibodies, CARCINOMA |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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