ES2B-C001 is a virus-like particle (VLP) vaccine against human HER-2 developed for the therapy of breast cancer. We show here that ES2B-C001 effectively inhibitsmammary carcinoma growth and metastasis in a transgenic mouse model expressing activated human HER-2. ES2B-C001 vaccine is a tag/catcher conjugation system:Acinectobacter phage 205 (AP205) capsid VLP, each with 180 tag peptides, are conjugated with catcher-HER-2 extracellular domain. The vaccine was administeredalone, thanks to the instrinsic adjuvanticity of the VLP, or with Montanide ISA 51. QD is a HER-2-positive cell line established from a mammary carcinoma of a Delta16(FVB background) transgenic mouse, bearing the human HER-2 splice variant Delta16. FVB female mice were challenged in the mammary fatpad with 1 million QDcells, vaccinations started 2 weeks after cell challenge and were repeated every 2 weeks. Untreated mice developed progressive tumors within one month, whereas70% of mice vaccinated without adjuvant and all mice vaccinated with adjuvant were still tumor-free after 7 months. Mice challenged intravenously (i.v.) developedmore than 300 lung metastasis, whereas all vaccinated mice remained metastasis-free. Delta16 transgenic mice are immunologically tolerant to human HER-2 anddevelop aggressive mammary carcinomas. Vaccination of young, tumor-free Delta16 mice completely prevented tumor onset for more than one year, whereas allcontrol mice developed progressive mammary carcinomas within 8 months of age. Delta16 mice challenged i.v. with QD cells mice developed a mean of 68 lungnodules, whereas 73% of mice vaccinated without adjuvant and all mice vaccinated with E2SB-C001+ISA 51 were free from metastases. Furthermore, twoadministrations of ES2B-C001+ISA 51 prevented spontaneous tumor onset in Delta16 mice for more than 1 year, while untreated mice developed mammarycarcinomas by 8 months of age. ES2B-C001 induced copious anti-HER-2 antibodies of all IgG subclasses, ranging 1-10 mg/mL in FVB mice and 0.1-1 mg/mL inDelta16 mice; antibody titers remained very high for 6-10 months after the last vaccination. Antibodies inhibited the 3D growth of human HER-2+++ and HER-2++breast cancer cells, of trastuzumab resistant cells and of gastric carcinoma cells. Vaccination increased interferon-gamma secreting cells in the spleen, as evaluated byELISPot (20.7±2.9 spots/2x10^5 cells. The results warrant further development of ES2B-C001 for the therapy of HER-2 positive human breast cancer and of other tumors expressing HER-2.

Ruzzi, F., Palladini, A., Clemmensen, S., Strobaek, A., Buijs, N., Domeyer, T., et al. (2023). Preclinical activity of ES2B-C001, a human candidate HER-2 virus-like particle (VLP) vaccine, against mammary carcinoma onset and metastasis. CANCER RESEARCH, 83(7), 687-687 [10.1158/1538-7445.AM2023-687].

Preclinical activity of ES2B-C001, a human candidate HER-2 virus-like particle (VLP) vaccine, against mammary carcinoma onset and metastasis

Ruzzi, F;Semprini, MS;Scalambra, L;Angelicola, S;Lollini, PL;
2023

Abstract

ES2B-C001 is a virus-like particle (VLP) vaccine against human HER-2 developed for the therapy of breast cancer. We show here that ES2B-C001 effectively inhibitsmammary carcinoma growth and metastasis in a transgenic mouse model expressing activated human HER-2. ES2B-C001 vaccine is a tag/catcher conjugation system:Acinectobacter phage 205 (AP205) capsid VLP, each with 180 tag peptides, are conjugated with catcher-HER-2 extracellular domain. The vaccine was administeredalone, thanks to the instrinsic adjuvanticity of the VLP, or with Montanide ISA 51. QD is a HER-2-positive cell line established from a mammary carcinoma of a Delta16(FVB background) transgenic mouse, bearing the human HER-2 splice variant Delta16. FVB female mice were challenged in the mammary fatpad with 1 million QDcells, vaccinations started 2 weeks after cell challenge and were repeated every 2 weeks. Untreated mice developed progressive tumors within one month, whereas70% of mice vaccinated without adjuvant and all mice vaccinated with adjuvant were still tumor-free after 7 months. Mice challenged intravenously (i.v.) developedmore than 300 lung metastasis, whereas all vaccinated mice remained metastasis-free. Delta16 transgenic mice are immunologically tolerant to human HER-2 anddevelop aggressive mammary carcinomas. Vaccination of young, tumor-free Delta16 mice completely prevented tumor onset for more than one year, whereas allcontrol mice developed progressive mammary carcinomas within 8 months of age. Delta16 mice challenged i.v. with QD cells mice developed a mean of 68 lungnodules, whereas 73% of mice vaccinated without adjuvant and all mice vaccinated with E2SB-C001+ISA 51 were free from metastases. Furthermore, twoadministrations of ES2B-C001+ISA 51 prevented spontaneous tumor onset in Delta16 mice for more than 1 year, while untreated mice developed mammarycarcinomas by 8 months of age. ES2B-C001 induced copious anti-HER-2 antibodies of all IgG subclasses, ranging 1-10 mg/mL in FVB mice and 0.1-1 mg/mL inDelta16 mice; antibody titers remained very high for 6-10 months after the last vaccination. Antibodies inhibited the 3D growth of human HER-2+++ and HER-2++breast cancer cells, of trastuzumab resistant cells and of gastric carcinoma cells. Vaccination increased interferon-gamma secreting cells in the spleen, as evaluated byELISPot (20.7±2.9 spots/2x10^5 cells. The results warrant further development of ES2B-C001 for the therapy of HER-2 positive human breast cancer and of other tumors expressing HER-2.
2023
Ruzzi, F., Palladini, A., Clemmensen, S., Strobaek, A., Buijs, N., Domeyer, T., et al. (2023). Preclinical activity of ES2B-C001, a human candidate HER-2 virus-like particle (VLP) vaccine, against mammary carcinoma onset and metastasis. CANCER RESEARCH, 83(7), 687-687 [10.1158/1538-7445.AM2023-687].
Ruzzi, F; Palladini, A; Clemmensen, S; Strobaek, A; Buijs, N; Domeyer, T; Dorosz, J; Soroka, V; Grzadziela, D; Rasmussen, CJ; Nielsen, IB; Soegaard, M...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/954646
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