Considerations for the clinical development of cytokine gene-transduced tumor cell vaccines.
In preclinical models, tumor cells genetically altered to secrete cytokines or express costimulatory molecules can generate systemic antitumor immunity. In some studies, these tumor vaccines have been shown to eradicate micrometastases. These results have led to the initiation of numerous phase I clinical trials employing either genetically modified or allogenic tumor vaccines. This article addresses a number of issues related to the clinical development of cytokine gene-transduced tumor cell vaccines including: (1) the production of cytokine-secreting tumor vaccines; and (2) the preclinical feasibility and toxicity studies required for testing these vaccines in patients with cancer.
Jaffee
E M
EM
The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Pardoll
D M
DM
D000818:Animals; D019496:Cancer Vaccines; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*
D019496:Cancer Vaccines; D016207:Cytokines