2.5: IL-2 is an immune mediator with a variety of effects on the function of 
the immune system. The effects have been described both in experimental 
animals and humans (33) . Injection of IL-2 can mediate antitumor immune 
responses against established tumors in patients with a variety of neoplastic 
diseases, notably malignant melanoma and renal cell cancer. IL-2 is essential 
for the development of "helper" function; it mediates expansion of the number 
of immunoreactive cells bearing IL-2 receptors. Established tumor cells are 
selectively killed following IL-2 administration (non malignant cells remain 
unaffected) . This supports the conclusion that structural differences between 
neoplastic and non-neoplastic cells are present; they can form the basis of a 
rational approach toward cancer immunotherapy. 
Why potentially antigenic tumors develop in immunocompetent individuals is not 
clear. Possibly, cells escape detection by the immune system even though they 
express determinants that are potential "targets" for recognition and 
destruction. Cytotoxic T lymphocytes are capable of recognizing an 
extraordinarily wide array of relatively small peptides derived from larger 
macromolecules in the context of membrane-associated structures specified by 
the Class I major histocompatability locus (MHC) . Therefore, the array of 
potential neoantigens is quite large and almost certainly includes neoantigens 
associated with primary and advanced neoplasms. Several lines of indirect 
evidence support the idea that progressively growing tumors remain 
unrecognized and do not undergo appropriate antigen processing. In inbred 
mice, a strong anti tumor immune response follows immunization of syngeneic 
recipients with tumor cells hybridized with cells expressing allogeneic MHC 
(34) . In an analogous manner, tumor cells modified by transfection and 
expression of genes specifying allogeneic antigens exhibit immunity toward 
nont ransf ected, syngeneic tumor cells (35-37) . Thus, the co-expression of 
foreign and weakly antigenic tumor-associated determinants provides a vehicle 
for recognition, antigen processing, and generation of an anti tumor immune 
response. At the same time, the expression of allogeneic MHC antigens 
protects the tumor-bearing recipient from the . malignant proliferation of the 
tumor cell vaccine itself , a possible danger if using viable tumor cell 
"vaccines" that are syngeneic with the host. Further evidence that the co- 
expression of foreign antigens along with tumor-associated determinants 
augments immune recognition is provided by the beneficial effects of 
immunizing experimental animals with tumor cells that have been infected with 
nonpathogenic viruses (9) or with viral constructs expressing tumor-associated 
determinants. Tumor-bearing animals immunized with such immunogens develop 
anti tumor immune responses that are capable of prolonging survival under 
circumstances in which the unmodified tumor cells themselves are not 
antigenic . 
Other approaches have been taken to modify tumor cells in order to increase 
the cells' antigenicity. In 1987, DNA from a highly malignant murine leukemia 
cell-line was transfected into a mouse fibroblast cell-line expressing defined 
allogeneic MHC antigens (35) . Like any foreign graft, the transfected cells 
were rejected by mice syngeneic with the tumor. Mice rejecting the 
transfected foreign cells exhibited strong anti tumor immune responses and 
survived longer following tumor challenge than non immunized mice. Tumor 
cells were killed by host immune mechanisms when the animals were challenged 
by injections of viable leukemia cells. Subsequently, DNA from mouse melanoma 
cells was transfected into fibroblasts expressing allogeneic MHC antigens 
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