NON-TECHNICAL ABSTRACT 
A Phase I Study of Vaccination with Autologous, Irradiated Melanoma Cells 
Engineered to Secrete Human Granulocyte-Macrophage Colony Stimulating 
Factor 
No consistently effective therapy exists for metastatic melanoma. Interest 
in the immunotherapy of melanoma has been stimulated by the observation 
of rare, spontaneous regressions of disease and the increasing evidence that 
the host can mount an immunologic response against melanoma. We have 
conducted extensive laboratory studies using a new strategy for inducing anti- 
tumor immune responses to mouse tumors, including melanoma. By 
inserting the immunostimulatory gene granulocyte-macrophage colony 
stimulating factor (GM-CSF) into mouse melanoma tumor cells and injecting 
them under the skin, systemic anti-tumor immune responses have been 
induced, resulting in the eradication of implanted tumors at distant sites. 
Importantly, the tumor vaccine cells could be lethally irradiated after genetic 
engineering without compromising the efficacy of treatment. We have 
demonstrated that this retroviral gene transfer system can also be used to 
introduce the GM-CSF gene into melanoma cells obtained from cancer 
patients. 
This clinical trial will evaluate the safety and toxicities associated with 
therapeutic vaccinations using autologous melanoma cells engineered to 
secrete human GM-CSF. Patients will undergo a surgical procedure to obtain 
melanoma cells for vaccine preparation. The patient cells will be genetically 
engineered to express the GM-CSF gene and then lethally irradiated. This 
represents an important safeguard against the introduction into the patient of 
tumor cells rendered potentially more virulent by laboratory manipulations. 
Patients will receive injections of the irradiated GM-CSF expressing cells in 
the skin. Different schedules of vaccination will be tested, ranging from 
injections every month to every week for a total of three months. 
The proposed study seeks to determine the safety and toxicity of 
administering this type of genetically engineered cancer vaccine. While the 
study is not intended to assess the efficacy of this treatment, it will provide 
important information that will be incorporated into future efficacy studies. 
Measurements will be made in this trial of any immunologic responses 
stimulated by the vaccine. 
Recombinant DNA Research, Volume 20 
[543] 
