Ex-vivo gene therapy using cytokine-transduced tumor vaccines: molecular and clinical pharmacology.
Whether the current generation of cytokine gene-transduced tumor vaccines will show clinical efficacy is under study. Fortunately, the large safety profile so far observed with gene-transduced tumor vaccines can allow outpatient testing in large populations of patients in the adjuvant therapy situation. This will allow large studies statistically powered to see potentially important adjuvant therapy effects in the range that are observed for tamoxifen in breast cancer. For example, the outpatient, adjuvant therapy safety context has been established in the use of GM-CSF gene-transduced autologous prostate cancer vaccines following radical prostatectomy. Similar adjuvant therapy clinical trial efforts are anticipated with allogeneic breast, colon, pancreatic, and ovarian cancer in addition to prostate, renal cell carcinoma, and melanoma. The reverse translation of early clinical data back to basic laboratory research also suggests the field of cytokine gene-transduced tumor vaccine research will remain vibrant. Efforts are currently being directed on optimizing DC activation with polycistronic constructs of cytokine genes, and overexpressing the most relevant tumor-associated peptides. As in the case of antineoplastic drug development, not all lead compounds will become approved drugs in medical oncology. Rigorous yet innovative clinical trial designs will be key to the accelerated identification of cytokine gene-transduced vaccines that improve survival in cancer patients.
Simons
J W
JW
Johns Hopkins Oncology Center, Brady Urological Institute, NIH SPORE in Prostate Cancer, Baltimore, MD 21287, USA.
Mikhak
B
B
D000818:Animals; D019496:Cancer Vaccines; D016207:Cytokines / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods / Q000639:trends; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends; D013601:T-Lymphocytes; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA
D019496:Cancer Vaccines; D016207:Cytokines; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor