Scientific Abstract 
SCIENTIFIC ABSTRACT 
Small-cell lung cancer is a fatal disease in more than 90% of affected patients despite 
combined modality therapy with radiation and chemotherapy. The intent of this protocol is to 
culture small-cell lung cancer cells and transfect them with the gene for Interleukin-2 (IL-2) 
production. These transfected cells will be returned to patients after cytoreduction of their 
cancer with conventional chemotherapy. The aim is for the reimplanted, IL-2 producing tumor 
cells to stimulate the proliferation of a tumor-specific population of cytotoxic lymphocytes 
capable of destroying the reimplanted tumor. The plasmid vector BMG-Neo is an efficient 
vector of transfection. It uses as a eukaryotic replication unit an 85.5 kb DNA fragment from 
the bovine papilloma virus 1. This plasmid replicates extra chromosomally as an episome 
producing a copy number of 20-100 per cell. In pre-clinical studies in a murine model using 
the Lewis lung carcinoma cell line, the administration of IL-2 transfected cancer cells led to 
rejection of subsequently administered non-transfected tumor cells and to regression of 
established tumors. In this study in humans, IL-2 transfected radiated (to prevent proliferation) 
tumor cells will be serially injected weekly over 4-6 weeks. Companion laboratory studies will 
seek to quantify and characterize the nature of the induced cytotoxic lymphocyte response in the 
patients’ peripheral blood. The laboratory component, in part, also will clone out populations 
of tumor specific lymphocytes for in vitro transfection studies of these cells. Clinical measures 
of response include regression of established tumor deposits and/or delay in time to disease 
progression. 
Recombinant DNA Research, Volume 18 
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