Inhibition of human tumor xenograft growth in nude mice by a conjugate of monoclonal antibody LA22 to epidermal growth factor receptor with anti-tumor antibiotics mitomycin C.
Anti-EGFR monoclonal antibodies LA22 and Erbitux bind to different epitopes of EGFR. The chemimmunoconjugates of MMC with LA22 or Erbitux were prepared, and in vitro cytotoxicity assays with A549 cells showed that LA22-MMC was much more potent than Erbitux or Erbitux-MMC. Viabilities of A549 cells treated with LA22-MMC, Erbitux or Erbitux-MMC were 35%, 94%, and 81%, respectively. Immunoscintigraphy of xenografts of human A431 and A549 cells in nude mice both showed that (125)I-labeled-LA22-MMC enriched in tumor sites prominently. Most importantly, in vivo assays showed LA22-MMC was significantly more effective than free drug MMC in the treatment of subcutaneous xenografts of human A431 cells in nude mice (83% inhibition for LA22-MMC and 30% for MMC). We concluded that LA22-MMC could be a very potent drug for treatment of solid tumors.
Shao
Wei
W
Welson Pharmaceuticals, Inc., 10239 Threadneedle CT, Ellicott City, MD 21042, USA.
Zhao
Shan
S
Liu
Zhaofei
Z
Zhang
Jianzhong
J
Ma
Shujun
S
Sato
J Denry
JD
Zhang
Peng
P
Tong
Mei
M
Han
Jiping
J
Wang
Yan
Y
Bai
Dongmei
D
Wang
Fan
F
Sun
Le
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D000068818:Cetuximab; D066246:ErbB Receptors / Q000737:chemistry*; D005260:Female; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000737:chemistry / Q000494:pharmacology*; D009368:Neoplasm Transplantation
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D016685:Mitomycin; D066246:ErbB Receptors; D000068818:Cetuximab