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vs Fc
RI-
1
*
Cancer Immunology, Peter MacCallum Cancer Institute, Victoria, Australia; and
Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital, Parkville, Victoria, Australia
The structurally related TCR-
and Fc receptor for IgE
(Fc
RI)-
are critical signaling components of the TCR and FcRI,
respectively. Although chimeric Ab receptors containing and
signaling chains have been used to redirect CTL to tumors, a direct
comparison of their relative efficacy has not previously been
undertaken. Here, in naive T lymphocytes, we compare the signaling
capacities of the and subunits within single-chain variable
domain (scFv) chimeric receptors recognizing the carcinoembryonic Ag
(CEA). Using a very efficient retroviral gene delivery system, high and
equivalent levels of scFv- and scFv- receptors were expressed in
T cells. Despite similar levels of expression and Ag-specific binding
to colon carcinoma target cells, ligation of scFv-anti-CEA-
chimeric receptors on T cells resulted in greater cytokine production
and direct cytotoxicity than activation via scFv-anti-CEA-
receptors. T cells expressing scFv- chimeric receptors had a greater
capacity to control the growth of human colon carcinoma in
scid/scid mice or mouse colon adenocarcinoma in
syngeneic C57BL/6 mice. Overall, these data are the first to directly
compare and definitively demonstrate the enhanced potency of T cells
activated via the signaling pathway.
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