Anti-tumoral potential of a human granulysin-based, CEA-targeted cytolytic immunotoxin
Granulysin is a protein present in the granules of human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, with cytolytic activity against microbes and tumors. Previous work demonstrated the therapeutic effect of intratumoral injection of recombinant granulysin using in vivo models of bre...
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doaj-ddae2382868c4a1a8515e30f3143a05f2020-11-25T03:24:39ZengTaylor & Francis GroupOncoImmunology2162-402X2019-11-0181110.1080/2162402X.2019.16413921641392Anti-tumoral potential of a human granulysin-based, CEA-targeted cytolytic immunotoxinRaquel Ibáñez-Pérez0Patricia Guerrero-Ochoa1Sameer Al-Wasaby2Rocío Navarro3Antonio Tapia-Galisteo4Diego De Miguel5Oscar Gonzalo6Blanca Conde7Luis Martínez-Lostao8Ramón Hurtado-Guerrero9Laura Sanz10Alberto Anel11Immunity and Cancer Group, University of Zaragoza/Aragón Health Research Institute (IIS-Aragón)Immunity and Cancer Group, University of Zaragoza/Aragón Health Research Institute (IIS-Aragón)Immunity and Cancer Group, University of Zaragoza/Aragón Health Research Institute (IIS-Aragón)“Puerta de Hierro” University Hospital“Puerta de Hierro” University HospitalImmunity and Cancer Group, University of Zaragoza/Aragón Health Research Institute (IIS-Aragón)Immunity and Cancer Group, University of Zaragoza/Aragón Health Research Institute (IIS-Aragón)Immunity and Cancer Group, University of Zaragoza/Aragón Health Research Institute (IIS-Aragón)“Lozano Blesa” University Clinical HospitalBiocomputation and Physics of Complex Systems Institute (BIFI), University of Zaragoza“Puerta de Hierro” University HospitalImmunity and Cancer Group, University of Zaragoza/Aragón Health Research Institute (IIS-Aragón)Granulysin is a protein present in the granules of human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, with cytolytic activity against microbes and tumors. Previous work demonstrated the therapeutic effect of intratumoral injection of recombinant granulysin using in vivo models of breast cancer and multiple myeloma. In the present work we have developed a granulysin gene fusion to the anti-carcinoembryonic antigen (CEA/CEACAM5) single chain Fv antibody fragment MFE23. Both granulysin and the granulysin-based immunotoxin were expressed in Pichia pastoris. The immunotoxin specifically recognized CEA, purified or expressed on the cell surface. Moreover, the bioactivity of the immunotoxin against several CEA+ cell lines was higher than that of granulysin alone. Granulysin and the immunotoxin were tested as a treatment in in vivo xenograft models in athymic mice. When injected intratumorally, both granulysin and the immunotoxin were able to inhibit tumor growth. Furthermore, systemic administration of the immunotoxin demonstrated a decrease in tumor growth in a CEA+ tumor-bearing mouse model, whereas granulysin did not exhibit a therapeutic effect. This is the first granulysin-based immunotoxin and the present work constitutes the proof of concept of its therapeutic potential.http://dx.doi.org/10.1080/2162402X.2019.1641392granulysinscfvimmunotoxinceacolon carcinoma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Raquel Ibáñez-Pérez Patricia Guerrero-Ochoa Sameer Al-Wasaby Rocío Navarro Antonio Tapia-Galisteo Diego De Miguel Oscar Gonzalo Blanca Conde Luis Martínez-Lostao Ramón Hurtado-Guerrero Laura Sanz Alberto Anel |
spellingShingle |
Raquel Ibáñez-Pérez Patricia Guerrero-Ochoa Sameer Al-Wasaby Rocío Navarro Antonio Tapia-Galisteo Diego De Miguel Oscar Gonzalo Blanca Conde Luis Martínez-Lostao Ramón Hurtado-Guerrero Laura Sanz Alberto Anel Anti-tumoral potential of a human granulysin-based, CEA-targeted cytolytic immunotoxin OncoImmunology granulysin scfv immunotoxin cea colon carcinoma |
author_facet |
Raquel Ibáñez-Pérez Patricia Guerrero-Ochoa Sameer Al-Wasaby Rocío Navarro Antonio Tapia-Galisteo Diego De Miguel Oscar Gonzalo Blanca Conde Luis Martínez-Lostao Ramón Hurtado-Guerrero Laura Sanz Alberto Anel |
author_sort |
Raquel Ibáñez-Pérez |
title |
Anti-tumoral potential of a human granulysin-based, CEA-targeted cytolytic immunotoxin |
title_short |
Anti-tumoral potential of a human granulysin-based, CEA-targeted cytolytic immunotoxin |
title_full |
Anti-tumoral potential of a human granulysin-based, CEA-targeted cytolytic immunotoxin |
title_fullStr |
Anti-tumoral potential of a human granulysin-based, CEA-targeted cytolytic immunotoxin |
title_full_unstemmed |
Anti-tumoral potential of a human granulysin-based, CEA-targeted cytolytic immunotoxin |
title_sort |
anti-tumoral potential of a human granulysin-based, cea-targeted cytolytic immunotoxin |
publisher |
Taylor & Francis Group |
series |
OncoImmunology |
issn |
2162-402X |
publishDate |
2019-11-01 |
description |
Granulysin is a protein present in the granules of human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, with cytolytic activity against microbes and tumors. Previous work demonstrated the therapeutic effect of intratumoral injection of recombinant granulysin using in vivo models of breast cancer and multiple myeloma. In the present work we have developed a granulysin gene fusion to the anti-carcinoembryonic antigen (CEA/CEACAM5) single chain Fv antibody fragment MFE23. Both granulysin and the granulysin-based immunotoxin were expressed in Pichia pastoris. The immunotoxin specifically recognized CEA, purified or expressed on the cell surface. Moreover, the bioactivity of the immunotoxin against several CEA+ cell lines was higher than that of granulysin alone. Granulysin and the immunotoxin were tested as a treatment in in vivo xenograft models in athymic mice. When injected intratumorally, both granulysin and the immunotoxin were able to inhibit tumor growth. Furthermore, systemic administration of the immunotoxin demonstrated a decrease in tumor growth in a CEA+ tumor-bearing mouse model, whereas granulysin did not exhibit a therapeutic effect. This is the first granulysin-based immunotoxin and the present work constitutes the proof of concept of its therapeutic potential. |
topic |
granulysin scfv immunotoxin cea colon carcinoma |
url |
http://dx.doi.org/10.1080/2162402X.2019.1641392 |
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