Antivector and tumor immune responses following adenovirus-directed enzyme prodrug therapy for the treatment of prostate cancer.
We have completed a phase I/II suicide gene therapy clinical trial in patients with prostate cancer, using an E1/E3-deleted replication-deficient adenovirus (CTL102) encoding the bacterial nitroreductase enzyme in combination with prodrug CB1954. This study has provided an opportunity to monitor and characterize vector- and tumor-specific adaptive immunity before and after single or repeat injections of adenovirus. Here we report robust vector-specific humoral and cellular immune responses in all patients monitored. However, we found no correlation between preexisting immunity or the magnitude of the immune response to vector and the clinical outcome as measured by changes in serum prostate-specific antigen (PSA) level. Increased frequency of T cells recognizing prostate-specific antigens PSA or prostate-specific membrane antigen (PSMA) was detected in 3 of 11 patients after therapy, suggesting that this direct cytotoxic strategy can also stimulate tumor-specific immunity.
Onion
David
D
Cancer Research UK Institute of Cancer Sciences, University of Birmingham, Birmingham, UK. d.f.onion@bham.ac.uk
Patel
Prashant
P
Pineda
Robert G
RG
James
Nicholas
N
Mautner
Vivien
V
D000256:Adenoviridae; D001388:Aziridines / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D041722:Genes, Transgenic, Suicide / Q000235:genetics* / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D009601:Nitroreductases; D011355:Prodrugs / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000097:blood / Q000276:immunology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology
D001388:Aziridines; D011355:Prodrugs; C100099:tretazicar; D007371:Interferon-gamma; D009601:Nitroreductases; D017430:Prostate-Specific Antigen