Induction of protective immunity against syngeneic rat cancer cells by expression of the cytosine deaminase suicide gene.
The use of the cytosine deaminase (CD)/5-fluorocytosine suicide system as a cancer gene therapy approach enables selective killing of CD-modified cells as well as the ablation of non-modified tumor cells due to a bystander effect that has been suggested to involve the immune system in vivo. Using a stable CD transfectant of the tumorigenic rat adenocarcinoma cell line AS (AS/CD), an antitumoral response against the CD expressing cell line as well as the parental cell line could be induced by stepwise vaccinations in syngeneic animals. AS/CD tumor regression occurred independently of 5-fluorocytosine treatment and was sufficient to protect 37% of the animals against subsequent challenge with tumorigenic doses of the parental AS cell line. Immune rats contained lymphocytes able to specifically lyse CD modified as well as unmodified AS tumor cells in vitro, most likely contributing to the in vivo antitumoral reaction. Thus, the CD suicide system seems to be suitable not only for a local tumor gene therapy but also for the application as therapy of metastatic tumors and minimal residual disease.
Haack
K
K
Sektion für Molekulare Diagnostik und Therapie, Chirurgische Universitätsklinik, Heidelberg, Germany.
Linnebacher
M
M
Eisold
S
S
Zöller
M
M
von Knebel Doeberitz
M
M
Gebert
J
J
D000230:Adenocarcinoma / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D000276:Adjuvants, Immunologic; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002857:Chromium / Q000737:chemistry; D043525:Cytosine Deaminase; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006735:Horseradish Peroxidase / Q000378:metabolism; D007111:Immunity, Cellular; D007114:Immunization / Q000379:methods*; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D009368:Neoplasm Transplantation; D009700:Nucleoside Deaminases / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D051381:Rats; D012680:Sensitivity and Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D015704:CD4 Antigens; D016827:CD8 Antigens; D002857:Chromium; D006735:Horseradish Peroxidase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase