cells but not normal cells (17^9^0). The LAK cells lyse tumor cells without 
preimmuni 2 :ation or MHC restriction (31). Interleukin-4 (IL-4) also generates LAK cells 
and acts synergistically with IL-2 in the generation of tumor sp>ecific killer cells (32). 
Since most malignancies arise in immunocompetent hosts, it is likely that tumor cells 
have evolved mechanism to escape host defenses, perhaps through evolution of 
successively less immunogenic clones (33). Deficient expression of class I MHC 
molecules limits the ability of tumor cells to present antigens to cytotoxic T cells. 
Freshly isolated cells from naturally occurring tumors frequently lack class I MHC 
antigen completely or show decreased expression (34-38). Reduced class I MHC 
expression could also facilitate growth of these tumors when transplanted into 
syngeneic recipients. Several tumor cell lines which exhibit low levels of class I MHC 
proteins become less oncogenic when expression vectors encoding the relevant class I 
MHC antigen cue introduced into them (39-43). In some experiments, tumor cells 
which express a class I MHC gene confer immunity in rudve recipients against the 
parental tumor (40,41). The absolute level of class I MHC expression however, is not 
the only factor which influences the tumorigenicity or immunogenidty of tumor cells. 
In one study, mouse mammary adenocarcinoma cells, treated with 5-azacytidine and 
selected for elevated levels of class I MHC expression did not display altered 
tumorigenicity compared to the parent line (44). 
The immune response to tumor cells can be stimulated by systemic administration of 
IL-2 (45), or IL-2 with LAK cells (46,47). Clinical trials using tumor infiltrating 
lymphocytes are also in progress (48). Recently, several studies have examined the 
tumor suppressive effect of lymphokine production by genetically altered tumor cells. 
The introduction of tumor cells traitsfected With an IL-2 expression vector into 
syngeneic mice stimulated an MHC class I restricted cytolytic T lymphocyte response 
which protected against subsequent rechallenge with the parental tumor cell line (49). 
Expression of 11-4 by plasmacytoma or mammary adenocarcinoma cells induced a 
potent cinti-tumor effect mediated by infiltration of eosinophils and macnrophages (50). 
These studies demonstrate that cytokines, expressed at high loc:al concentrations, are 
effective anti-tumor agents. 
Nabel 2 uid <x>-workers have previously projX)sed an alternative approach to stimulate 
an anti-tumor response, through the intrcxiuction of an allogeneic cdass I MHC gene 
into established humcui tumors. The antigenicity of tumor cells has been altered 
previously by the expression of viral antigens through infection of tumor cells (51-55), 
or expression of allogeneic antigens intrc^uced by somatic cell hybridization (56,57). 
Allogeneic cdass I MHC genes have been introduced into tumor cells by transfection 
and subsequent selection in vitro. These exp>eriments have prcxiuced some conflicting 
results. In one case, transfecdion of an allogeneic cdass I MHC gene (H-2L^) into an H- 
2^ tumor resulted in immunologic rejection of the transduced cells and also produced 
transplantation resistance against the pcirent tumor cells (58). In another instance, 
Recombinant DNA Research, Volume 19 
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