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 are introduced into them (39-43). In some experiments, tumor cells 
which express a class I MHC gene confer immunity in naive 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 immunogenicity 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 transfected 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 anti-tumor effect mediated by infiltration of eosinophils and macrophages (50). 
These studies demonstrate that cytokines, expressed at high local concentrations, are 
effective anti-tumor agents. 
Nabel and co-workers have previously proposed an alternative approach to stimulate 
an anti-tumor response, through the introduction of an allogeneic class I MHC gene 
into established human 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 introduced by somatic cell hybridization (56,57). 
Allogeneic class I MHC genes have been introduced into tumor cells by transfection 
and subsequent selection in vitro. These experiments have produced some conflicting 
results. In one case, transfection of an allogeneic class 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 parent tumor cells (58). In another instance, 
transfection of H-2^ melanoma cells with the H-2D^ gene did not lead to rejection (59), 
however increased differential expression of H-2D products relative to H-2K may have 
affected the metastatic potential and immunogenicity of tumor cells (60). The effects of 
allogeneic H-2K gene expression in tumor cells was examined in another study (61). 
Several subclones which were selected in vitro and expressed an allogeneic gene were 
rejected in mice syngeneic for the parental tumor line, however, other subclones did not 
differ from the parental, untransduced line in generating tumors. This finding suggests 
that clone-to-clone variation in in vivo growth and tumorigenic capacity may result in 
other modifications of cells caused by transfection or the subcloning procedure, which 
affects their tumorgenicity. These types of clonal differences would likely be 
minimized by transducing a population of cells directly in vivo. 
Recombinant DNA Research, Volume 18 
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