abrogation of tumorigenic activity was eliminated when mice were immuno- 
suppressed by irradiation. We have now extended these results to the very- 
poorly immunogenic MCA-102 tumor. We have been unable to generate in vivo 
immunity against this tumor despite many attempts. Using retroviral vectors 
the IL-2 gene was transduced into the MCA-102 tumor and clones of IL-2 
producing MCA-102 tumor were developed. IL-2 production was stable for over 
three months (Fig. 2). The introduction and expression of the IL-2 gene into 
these tumors abrogated their ability to generate subcutaneous tumors in 
syngeneic mice and could also cause the reduction in growth of nontransduced 
tumor at the same site (Fig. 3). The immunologic nature of this immune 
reaction was demonstrated by showing that IL-2 transduced tumors could grow in 
irradiated mice or in mice that were depleted of CD8+ cells. It thus appears 
that in syngeneic mice the injection of IL-2 modified tumor cells could induce 
an immunity sufficient to cause the spontaneous regression of these IL-2 gene 
modified tumor cells as well as normal tumor cells mixed at the same site. 
In this proposal we plan to take advantage of the increased 
immunogenic ity of these IL-2 producing tumors to attempt to immunize patients 
with advanced and otherwise untreatable metastatic cancer. These tumor cells 
will be injected subcutaneously and intradermally into the thigh in an area 
that can be followed easily in an attempt to both immunize the patient against 
their cancer as well as to provide local immunization that could be used to 
grow lymphocytes for use in adoptive therapy. Lymphocytes will be obtained 
either from the draining inguinal lymph node group or from the tumor site 
itself. 
In addition to the increased immunogenic ity of the gene modified tumor, 
recent work in the Surgery Branch has suggested that the subcutaneous 
injection of tumor can lead to the development of more effective tumor 
infiltrating lymphocytes. In 12 successive experiments, TIL grown from 
visceral sites were simultaneously tested by careful in vivo titration against 
TIL from tumor injected into the cutaneous site. In 11 of 12 experiments, TIL 
from the subcutaneous location were more effective than those at visceral 
Recombinant DNA Research, Volume 15 
[109] 
