RT Journal Article
SR Electronic
T1 Tumor-specific Anti-Epidermal Growth Factor Receptor Variant III Monoclonal Antibodies: Use of the Tyramine-Cellobiose Radioiodination Method Enhances Cellular Retention and Uptake in Tumor Xenografts
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 4375
OP 4382
VO 55
IS 19
A1 Reist, Craig J.
A1 Archer, Gary E.
A1 Kurpad, Shekar N.
A1 Wikstrand, Carol J.
A1 Vaidyanathan, Ganesan
A1 Willingham, Mark C.
A1 Moscatello, David K.
A1 Wong, Albert J.
A1 Bigner, Darell D.
A1 Zalutsky, Michael R.
YR 1995
UL http://cancerres.aacrjournals.org/content/55/19/4375.abstract
AB Amplification and rearrangement of the epidermal growth factor receptor (EGFR) gene are characteristics of many types of tumors. One class of EGFR mutations, EGFRvIII, is characterized by an in-frame deletion resulting in a truncated external domain of the receptor. EGFR-vIII was first identified in a subset of gliomas and has since been found in some non-small cell lung carcinomas and breast carcinomas. mAbs specific for this variant form of EGFR but unreactive with the wild-type EGFR have been reported from our laboratory. This study further characterizes three of these antibodies. We determined, via radiolabeling techniques and immunofluorescence microscopy, that, after cell binding in vitro, the anti-EGFRvIII-specific mAbs internalize at 37°C. Furthermore, subsequent to internalization, the antibodies were processed intracelluarly, presumably by lysosomal degradation. We also examined the use of an alternative radiolabeling procedure that uses nonmetabolizable radioiodinated tyramine cellobiose. Our results show that the tyramine cellobiose labeling method allows for greater tumor cell retention of radiolabel in vitro (76% for tyramine cellobiose and 27% for Iodo-Gen after 24 h). Paired-label biodistribution studies in athymic mice indicate that anti-EGFRvIII mAb L8A4 localizes specifically to EGFRvIII-expressing tumor xenografts with a maximum of 34.3 ± 7.6% injected dose/g when labeled using tyramine collobiose compared with a maximum of 14.9 ± 4.3% injected dose/g using Iodo-Gen; similar results were obtained with mAb H10. These results suggest that the anti-EGFRvIII mAbs may serve as potential carriers for radioconjugate- and immunotoxin-based therapies for tumors expressing EGFRvIII. ©1995 American Association for Cancer Research.