Targeting human cytotoxic T lymphocytes to kill heterologous epidermal growth factor receptor-bearing tumor cells. Tumor-infiltrating lymphocyte/hormone receptor/recombinant antibody
Gillies, S.D.; Wesolowski, J.S.; Lo, K.M.
Journal of Immunology 146(3): 1067-1071
1991
ISSN/ISBN: 0022-1767 PMID: 1824849 Document Number: 387684
A genetically engineered conjugate between an anti-CD3 antibody and epidermal growth factor (EGF) was tested for its ability to mediate the lysis of receptor-bearing cells by human CTL. This construct was made by fusing an EGF coding sequence to the 3' end of the human gamma-1 H chain gene sequence and expressing the modified gene in transfected cells together with the V regions of a mouse antibody specific for the human T cell marker, CD3. The resulting conjugate was able to compete with EGF for its receptor and, at extremely low concentrations, was able to mediate the lysis of receptor-bearing tumor targets by a tumor-infiltrating lymphocytes line or by a CTL line established from peripheral blood. The construction of such conjugates by genetic engineering represents a general approach to the direct expression of highly specific hetero-bifunctional reagents without the necessity of further in vitro manipulations.