A liposome-based cancer vaccine for a rapid and high-titre anti-ErbB-2 antibody response

Vaccines are arguably the most important medical technology developed to date. However, effective treatment of diseases such as breast cancer have so far evaded standard vaccination strategies. One popular target for cancer treatment is the cell surface membrane protein, ErbB-2, also known as Her-2...

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Veröffentlicht in:European journal of pharmaceutical sciences 2020-09, Vol.152, p.105456-105456, Article 105456
Hauptverfasser: Wallis, Jamie, Katti, Prateek, Martin, Alexander M., Hills, Tom, Seymour, Leonard W., Shenton, Daniel P., Carlisle, Robert C.
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container_title European journal of pharmaceutical sciences
container_volume 152
creator Wallis, Jamie
Katti, Prateek
Martin, Alexander M.
Hills, Tom
Seymour, Leonard W.
Shenton, Daniel P.
Carlisle, Robert C.
description Vaccines are arguably the most important medical technology developed to date. However, effective treatment of diseases such as breast cancer have so far evaded standard vaccination strategies. One popular target for cancer treatment is the cell surface membrane protein, ErbB-2, also known as Her-2 or neu. It is localised to the cell surface and has raised expression in 15–30% of all breast cancers, as well as in ovarian, colon and lung cancer. Here, a liposomal system comprised of spatially separated ErbB-2 peptide, to activate B cells, and ovalbumin peptide OVA323−339, to provide non-cognate T cell support, was used to generate antibodies against the epitope of the ErbB-2 protein targeted by Pertuzumab, a monoclonal antibody licensed for the treatment of ErbB-2 expressing cancers. After just 7 days a raised (7.3-fold, p
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However, effective treatment of diseases such as breast cancer have so far evaded standard vaccination strategies. One popular target for cancer treatment is the cell surface membrane protein, ErbB-2, also known as Her-2 or neu. It is localised to the cell surface and has raised expression in 15–30% of all breast cancers, as well as in ovarian, colon and lung cancer. Here, a liposomal system comprised of spatially separated ErbB-2 peptide, to activate B cells, and ovalbumin peptide OVA323−339, to provide non-cognate T cell support, was used to generate antibodies against the epitope of the ErbB-2 protein targeted by Pertuzumab, a monoclonal antibody licensed for the treatment of ErbB-2 expressing cancers. After just 7 days a raised (7.3-fold, p&lt;0.01), isotype-switched, humoral immune response specific for the ErbB-2 peptide was achieved in mice with pre-existing immunity to OVA which were exposed to liposomes with external ErbB-2 and internal OVA323−339. The absence of pre-existing OVA immunity in the mice or OVA323−339 peptide in the liposomes removed the effect. The effect of this anti-ErbB-2 antibody response was characterised against an ErbB-2 overexpressing tumour cell line both in vitro and in vivo. Notably, antibody responses were demonstrated to induce cell death in vitro, resulting in 96% reduction in viable cells. This study, therefore, demonstrates the feasibility of this approach to generate a rapid, high-titre, isotype-switched, antibody response that specifically targets ErbB-2 overexpression on tumour cells and is capable of inducing cell death in vitro in the absence of complement or immune cells. 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subjects Animals
Antibodies, Monoclonal
Antibody Formation
Cancer
Cancer Vaccines
Cell Line, Tumor
ErbB2
Her2
Liposome
Liposomes
Mice
Neoplasms - drug therapy
Receptor, ErbB-2
Vaccination
Vaccine
title A liposome-based cancer vaccine for a rapid and high-titre anti-ErbB-2 antibody response
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