Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma

Abstract A promising therapy for patients with B-cell lymphoma is based on vaccination with idiotype monoclonal antibodies (mAbs). Since idiotypes are different in each tumor, a personalized vaccine has to be produced for each patient. Expression of immunoglobulins with appropriate post-translationa...

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Autores principales:	Erkuden Casales, Eva Martisova, Helena Villanueva, Ascensión López Díaz de Cerio, Susana Inoges, Noelia Silva-Pilipich, María Cristina Ballesteros-Briones, Alejandro Aranda, Jaione Bezunartea, Maurizio Bendandi, Fernando Pastor, Cristian Smerdou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/417560bac2294dd7a488e4ad9bd7d759
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spelling	oai:doaj.org-article:417560bac2294dd7a488e4ad9bd7d7592021-11-08T10:51:17ZIdiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma10.1038/s41598-021-00787-52045-2322https://doaj.org/article/417560bac2294dd7a488e4ad9bd7d7592021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00787-5https://doaj.org/toc/2045-2322Abstract A promising therapy for patients with B-cell lymphoma is based on vaccination with idiotype monoclonal antibodies (mAbs). Since idiotypes are different in each tumor, a personalized vaccine has to be produced for each patient. Expression of immunoglobulins with appropriate post-translational modifications for human use often requires the use of stable mammalian cells that can be scaled-up to reach the desired level of production. We have used a noncytopathic self-amplifying RNA vector derived from Semliki Forest virus (ncSFV) to generate BHK cell lines expressing murine follicular lymphoma-derived idiotype A20 mAb. ncSFV/BHK cell lines expressed approximately 2 mg/L/24 h of A20 mAb with proper quaternary structure and a glycosylation pattern similar to that of A20 mAb produced by hybridoma cells. A20 mAb purified from the supernatant of a ncSFV cell line, or from the hybridoma, was conjugated to keyhole limpet hemocyanin and used to immunize Balb/c mice by administration of four weekly doses of 25 µg of mAb. Both idiotype mAbs were able to induce a similar antitumor protection and longer survival compared to non-immunized mice. These results indicate that the ncSFV RNA vector could represent a quick and efficient system to produce patient-specific idiotypes with potential application as lymphoma vaccines.Erkuden CasalesEva MartisovaHelena VillanuevaAscensión López Díaz de CerioSusana InogesNoelia Silva-PilipichMaría Cristina Ballesteros-BrionesAlejandro ArandaJaione BezunarteaMaurizio BendandiFernando PastorCristian SmerdouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Erkuden Casales Eva Martisova Helena Villanueva Ascensión López Díaz de Cerio Susana Inoges Noelia Silva-Pilipich María Cristina Ballesteros-Briones Alejandro Aranda Jaione Bezunartea Maurizio Bendandi Fernando Pastor Cristian Smerdou Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma
description	Abstract A promising therapy for patients with B-cell lymphoma is based on vaccination with idiotype monoclonal antibodies (mAbs). Since idiotypes are different in each tumor, a personalized vaccine has to be produced for each patient. Expression of immunoglobulins with appropriate post-translational modifications for human use often requires the use of stable mammalian cells that can be scaled-up to reach the desired level of production. We have used a noncytopathic self-amplifying RNA vector derived from Semliki Forest virus (ncSFV) to generate BHK cell lines expressing murine follicular lymphoma-derived idiotype A20 mAb. ncSFV/BHK cell lines expressed approximately 2 mg/L/24 h of A20 mAb with proper quaternary structure and a glycosylation pattern similar to that of A20 mAb produced by hybridoma cells. A20 mAb purified from the supernatant of a ncSFV cell line, or from the hybridoma, was conjugated to keyhole limpet hemocyanin and used to immunize Balb/c mice by administration of four weekly doses of 25 µg of mAb. Both idiotype mAbs were able to induce a similar antitumor protection and longer survival compared to non-immunized mice. These results indicate that the ncSFV RNA vector could represent a quick and efficient system to produce patient-specific idiotypes with potential application as lymphoma vaccines.
format	article
author	Erkuden Casales Eva Martisova Helena Villanueva Ascensión López Díaz de Cerio Susana Inoges Noelia Silva-Pilipich María Cristina Ballesteros-Briones Alejandro Aranda Jaione Bezunartea Maurizio Bendandi Fernando Pastor Cristian Smerdou
author_facet	Erkuden Casales Eva Martisova Helena Villanueva Ascensión López Díaz de Cerio Susana Inoges Noelia Silva-Pilipich María Cristina Ballesteros-Briones Alejandro Aranda Jaione Bezunartea Maurizio Bendandi Fernando Pastor Cristian Smerdou
author_sort	Erkuden Casales
title	Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma
title_short	Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma
title_full	Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma
title_fullStr	Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma
title_full_unstemmed	Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma
title_sort	idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying rna vector induce antitumor responses in a murine model of b-cell lymphoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/417560bac2294dd7a488e4ad9bd7d759
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Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma

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