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

Journal Article · Fri Oct 20 00:00:00 EDT 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.08.114· OSTI ID:20854533

Wei, Shao ^[1]; Shan, Zhao ^[1]; Zhaofei, Liu ^[2]; Jianzhong, Zhang ^[3]; Shujun, Ma ^[1]; Sato, J Denry ^[4]; Peng, Zhang ^[1]; Mei, Tong ^[1]; Jiping, Han ^[5]; Yan, Wang ^[5]; Dongmei, Bai ^[5]; Fan, Wang ^[2]; Le, Sun ^[1]

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1. Welson Pharmaceuticals, Inc., 10239 Threadneedle CT, Ellicott City, MD 21042 (United States)
2. Medical Isotopes Research Center, Peking University, 38 Xueyuan Rd, Beijing 100083 (China)
3. Department of Pathology, Beijing 306 Hospital, 9 North Anxing Rd, Beijing 100101 (China)
4. Mountain Desert Island Biological Laboratory, Salisbury Cove, ME 04672 (United States)
5. Employee's Hospital of CNPC Liaoyang Petrochemical Fiber Company, 5 Gongnong Ave, Liaoyang, Liaoning (China)

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 {sup 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.

• OSTI ID: 20854533
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 349, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2006.08.114; PII: S0006-291X(06)01928-0; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL GROWTH
GROWTH FACTORS
IMMUNOTHERAPY
IN VITRO
IN VIVO
INHIBITION
IODINE 125
MICE
MITOMYCIN
MONOCLONAL ANTIBODIES
NEOPLASMS
RECEPTORS
TOXICITY