Anti-tumoral potential of a human granulysin-based, CEA-targeted cytolytic immunotoxin
| Autor: | Ramon Hurtado-Guerrero, Blanca Conde, Laura Sanz, Antonio Tapia-Galisteo, Raquel Ibáñez-Pérez, Alberto Anel, Luis Martínez-Lostao, Diego de Miguel, Sameer Al-Wasaby, Rocío Navarro, Patricia Guerrero-Ochoa, Oscar Gonzalo |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Immunology colon carcinoma lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Antigen In vivo Immunotoxin Immunology and Allergy Cytotoxic T cell Granulysin Original Research Chemistry granulysin lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens scfv immunotoxin Cytolysis CTL 030104 developmental biology Oncology cea 030220 oncology & carcinogenesis Systemic administration Cancer research lcsh:RC581-607 |
| Zdroj: | OncoImmunology, Vol 8, Iss 11 (2019) Oncoimmunology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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