Non-Technical Abstract 
NON-TECHNICAL ABSTRACT 
This study involves the use of novel methods to treat patients with metastatic 
melanoma by manipulation of their immune system. Based on extensive animal studies, we 
know that the immune system has the potential to recognize tumor cells as being foreign to 
the body and destroy them. The critical component of the immune system which appears to 
be involved in the rejection of tumors are lymphocytes. The ability to generate these 
lymphocytes in the laboratory would be useful for potential therapy of cancer. This approach 
has been called adoptive immunotherapy and involves the infusion of cancer reactive 
lymphocytes into patients in order to cause tumor shrinkage. 
Unfortunately, the generation of immune lymphocytes which can reject human cancers 
has been extremely difficult. One possible reason why this problem exists is that the foreign 
proteins present on human tumor cells are very weak in their ability to stimulate the immune 
system to react against them. Based on our animal studies, we have devised an approach to 
artificially stimulate immune cells that may be used for the treatment of human tumors that 
under normal circumstances would not occur. This involves a two-step process. The first 
step requires vaccination of the patient with their own tumor cells which have previously been 
removed and genetically engineered to secrete an immune factor called interleukin 4 (IL-4). 
The tumor cells are irradiated prior to injection into the skin in order to prevent outgrowth of 
tumor at the site. It has been found in animal studies that the production of IL-4 by the gene- 
modified tumor cells promotes an immune response in lymph nodes near the vaccination 
site. Lymph nodes are small glands of the immune system where lymphocytes congregate. 
The lymph nodes adjacent to the vaccination sites will be surgically removed approximately 7 
to 10 days later and taken to the laboratory for further processing. In the laboratory, cells from 
the lymph nodes will be stimulated and grown in special flasks by methods we have 
previously described for a 2 to 3 week period in order to generate a large number of immune 
lymphocytes. These lymphocytes will be collected and infused back into the patient along 
with the administration of interleukin-2, another immune protein. The interleukin-2 has been 
found to promote the antitumor effect of the immune lymphocytes in cancer patients. 
This clinical study proposes to address several important questions. These questions 
include: 1) Can this clinical treatment program be performed as described and what are its 
side-effects, 2) What antitumor response can be seen with this treatment, and 3) What is the 
immunological function of the immune lymphocytes, as assessed by laboratory tests. 
Recombinant DNA Research, Volume 18 
[781] 
