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Interleukin-2-transduced lymphocytes grow in an autocrine fashion and
remain responsive to antigen
J Treisman, P Hwu, S Minamoto, GE Shafer, R Cowherd, RA Morgan and SA Rosenberg
Surgery Branch, National Cancer Institute, National Institutes of Health,
Bethesda, MD 20892.
The maintenance of T lymphocytes in vivo after adoptive transfer for
immunotherapy requires the systemic administration of interleukin-2 (IL-
2), but prolonged administration of IL-2 is associated with substantial
toxicity. The constitutive production of IL-2 by T cells may be an
alternative method to prolong T-cell survival and potentially augment
antitumor responses. To study the effects of constitutive production of
IL-2 on the growth and antigen reactivity of a murine T cell, the sperm-
whale myoglobin (SWM) specific T-cell line 14.1 was retrovirally transduced
with the cDNA for IL-2. Cells that were transduced with vectors without an
internal promoter were able to proliferate in the absence of exogenously
added IL-2, and to grow in an autocrine fashion. These vectors used an
internal ribosomal entry site (IRES) to allow translation of the neomycin
phosphotransferase (neor) gene. In contrast, the cells transduced with an
IL-2 vector in which the neor gene was under the transcriptional control of
an internal SV-40 promoter failed to proliferate or grow in the absence of
exogenously added IL-2. The proliferation of the cells growing without IL-2
could be inhibited with antibodies to the IL-2 receptor or to human IL-2,
indicating that they were still IL-2 dependent. Despite their autocrine
growth, no tumor formation was observed in syngeneic mice injected
subcutaneously with the transduced cells, and the cells retained their
antigen reactivity and specificity. These results suggest that autocrine
growth of T cells for therapy will not interfere with effector function.
Volume 85,
Issue 1,
pp. 139-145,
01/01/1995
Copyright © 1995 by The American Society of Hematology
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