Recombinant antibody toxins specific for ERBB2 and EGF receptor inhibit the in vitro growth of human head and neck cancer cells and cause rapid tumorregression in vivo
M. Azemar et al., Recombinant antibody toxins specific for ERBB2 and EGF receptor inhibit the in vitro growth of human head and neck cancer cells and cause rapid tumorregression in vivo, INT J CANC, 86(2), 2000, pp. 269-275
Overexpression of the ErbB2 and epidermal growth factor receptor (EGFR) tyr
osine kinases is frequently observed in squamous cell carcinomas of the hea
d and neck, and has been correlated with shorter overall survival. By immun
oblot analysis, we have found EGFR and ErbB2 expression in 6 out of 6 estab
lished head and neck cancer cell lines. Elevated ECFR protein levels were n
oted in 3 and elevated ErbB2 levels in 5 of them. Significant expression of
EGFR and ErbB2 was also detected in 17 of 47 and 26 of 45 primary tumor sa
mples. Due to their enhanced expression on the tumor cell surface, these re
ceptors can be regarded as suitable targets for directed cancer therapy. We
have analyzed the antitumoral activity of recombinant single-chain antibod
y toxins specific for ErbB2 and EGFR against head and neck cancer cells in
vitro and in vivo, The recombinant toxins consist of the variable domains o
f the heavy and light chains of monoclonal antibodies (MAbs) genetically fu
sed to a truncated Pseudomonas exotoxin A (ETA), At low concentrations, the
ErbB2-specific single-chain antibody (scFv) toxin scFv(FRP5)-ETA and the E
GFR-specific toxins scFv(225)-ETA and scFv(14E1)-ETA inhibited the in vitro
growth of established head and neck cancer cell lines and primary tumor ce
lls. In a nude mouse tumor model, intratumoral injection of the antibody to
xins resulted in the rapid regression of subcutaneously growing CAL 27 tumo
r xenografts, with scFv(FRP5)-ETA and scFv(14E1)-ETA treatment being most e
ffective and leading to the cure of up to 50% of the animals. Our results s
uggest that EGFR and ErbB2-specific antibody toxins may become valuable the
rapeutic reagents for the treatment of squamous cell carcinomas of the head
and neck. Int. J, Cancer 86: 269-275, 2000. (C) 2000 Wiley-Liss, Inc.