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
Creators
- 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)
Description
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 125I-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
Additional details
Identifiers
- DOI
- 10.1016/j.bbrc.2006.08.114;
- PII
- S0006-291X(06)01928-0;
Publishing Information
- Journal Title
- Biochemical and Biophysical Research Communications
- Journal Volume
- 349
- Journal Issue
- 2
- Journal Page Range
- p. 816-824
- ISSN
- 0006-291X
- CODEN
- BBRCA9
INIS
- Country of Publication
- United States
- Country of Input or Organization
- International Atomic Energy Agency (IAEA)
- INIS RN
- 38027523
- Subject category
- S60: APPLIED LIFE SCIENCES;
- Descriptors DEI
- ANIMAL GROWTH; GROWTH FACTORS; IMMUNOTHERAPY; IN VITRO; IN VIVO; INHIBITION; IODINE 125; MICE; MITOMYCIN; MONOCLONAL ANTIBODIES; NEOPLASMS; RECEPTORS; TOXICITY
- Descriptors DEC
- ANIMALS; ANTI-INFECTIVE AGENTS; ANTIBIOTICS; ANTIBODIES; ANTIMITOTIC DRUGS; ANTINEOPLASTIC DRUGS; BETA DECAY RADIOISOTOPES; DAYS LIVING RADIOISOTOPES; DISEASES; DRUGS; ELECTRON CAPTURE RADIOISOTOPES; GROWTH; INTERMEDIATE MASS NUCLEI; INTERNAL CONVERSION RADIOISOTOPES; IODINE ISOTOPES; ISOTOPES; MAMMALS; MEDICINE; MEMBRANE PROTEINS; MITOGENS; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; PROTEINS; RADIOISOTOPES; RODENTS; THERAPY; VERTEBRATES
Optional Information
- Copyright
- Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.