Abstract:
: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.
journal_name
Oncoimmunologyjournal_title
Oncoimmunologyauthors
Ibáñez-Pérez R,Guerrero-Ochoa P,Al-Wasaby S,Navarro R,Tapia-Galisteo A,De Miguel D,Gonzalo O,Conde B,Martínez-Lostao L,Hurtado-Guerrero R,Sanz L,Anel Adoi
10.1080/2162402X.2019.1641392subject
Has Abstractpub_date
2019-07-22 00:00:00pages
1641392issue
11eissn
2162-4011issn
2162-402Xpii
1641392journal_volume
8pub_type
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