Cancer and Genetic Modification of Biologic Control 
IL, stemming from a time when they were called 
"interleukins," or agents that mediated signals 
between white blood cells, or leukocytes.) IL-4 
has several cell-signaling functions that have 
been recognized by studies in tissue culture. Al- 
though its precise role in the body has not been 
proved, IL-4 is suspected of playing a role in mod- 
ulating the immune response. IL-7 is thought to 
have a major role in the orderly development of 
antibody-producing cells, the so-called B cells. 
To learn what role, if any, these interleukins 
play in modulating the body's response to cancer, 
we devised a powerful test for their function as 
antitumor agents. We planted the gene for IL-4 in 
a tumor cell that allowed its high-level produc- 
tion. The IL-4-producing tumor grew well in a 
tissue culture dish, suggesting that IL-4 did not 
directly block growth of the tumor cell. How- 
ever, when the IL-4-producing tumor was trans- 
planted to a host mouse, the tumor growth was 
completely blocked. Evidently IL-4 was eliciting 
a host defense mechanism that prevented tumor 
growth. We have extended this observation to 
many different types of tumor cells under many 
conditions and have obtained similarly dramatic 
results. 
Further studies of the antitumor action of IL-4 
have allowed us to identify two particular cell 
types that may be mediating this antitumor effect. 
One of these is the eosinophil, a cell that is in- 
volved in many allergic responses. The second 
candidate mediator cell is the macrophage, a scav- 
enger cell concerned with many cell-killing 
functions. Our most recent work has focused on 
the particularly esoteric eosinophil, a cell 
thought to be involved in defense against para- 
sitic diseases and in certain allergic disorders. 
Studies using specific reagents now convince us 
that this peculiar cell is the major mediator of the 
antitumor effect. 
We would also like to know whether a small 
increase in the production of IL-4 can influence 
an organism's ability to develop or defend itself 
against malignancy. Accordingly, we made trans- 
genic mice that carry extra copies of the IL-4 gene 
to ensure that their lymphocytes produce large 
amounts of this agent. Creating these mice 
proved quite difficult, since high concentrations 
of IL-4 have an extremely disruptive influence on 
the murine immune system. We solved this prob- 
lem by creating a graded set of transgenic mice 
that yielded reduced levels of IL-4. By means of 
special regulatory gene signals, we were able to 
create mice that produced IL-4 in minimally 
disruptive amounts. From these animals we have 
learned that IL-4 has a profound influence on the 
immune cells that develop in the thymus gland, a 
key organ in the immune system. But we have also 
seen that this lymphokine can induce a serious 
allergic inflammatory response, suggesting that 
we will have to deal with this side effect before 
considering the therapeutic uses of this agent. 
We have expanded these studies to view the 
actions of other lymphokines that, theoretically, 
might influence tumor occurrence. Our prelimi- 
nary studies indicate that IL-7 may provoke a tu- 
mor-inducing response, clearly indicating that 
different growth signals can have dramatically 
different effects in the organism. 
Finally, although this brief account cannot 
cover the entire range of our studies, we have 
turned to a third element (the so-called kit li- 
gand), which has a profound influence on the 
development of cells during the formation of the 
embryo. This factor influences the development 
of cells that contribute to the formation of blood, 
of pigment-producing cells, and of eggs and 
sperm. In other words, if a mouse cannot make 
this element, it is sterile, albino, and has a pro- 
found anemia. Because we feel that the develop- 
mental pathway a cell follows strongly influences 
its propensity to undergo a malignant change, we 
are studying this factor to learn how it influences 
this important process in the mouse. 
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