Unsuitability of monoclonal antibodies to oncogene proteins for anti-tumour drug-targeting.
Monoclonal antibodies (MAbs) to ras, sis, erb-B, src, myb and myc oncoproteins were evaluated for their potential to target anti-cancer drugs to malignant cells. Each antibody was tested for reactivity against both fixed and viable cultured human tumour cells by immunofluorescence, and all reacted against a variety of fixed tumour cell preparations. Reactions were also observed against fixed non-malignant cells. None, however, reacted significantly with viable cells. Two antibodies (against ras and myc proteins) were tested for their ability to localize to tumour xenografts in nude mice, and conjugates were constructed by linking these antibodies to methotrexate using human serum albumin as an intermediate carrier. Neither antibody localized to tumour in vivo, and the methotrexate conjugates were not significantly cytotoxic for tumour cells in vitro, in contrast to similar conjugates simultaneously prepared with a proven anti-tumour MAb (791T/36). It was concluded that currently available MAbs to oncogene proteins are not suitable vectors for targeting cytotoxic agents to tumour cells.
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006801:Humans; D007457:Iodine Radioisotopes; D008727:Methotrexate / Q000008:administration & dosage; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000276:immunology; D012235:Rhodamines; D012709:Serum Albumin / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D011518:Proto-Oncogene Proteins; D012235:Rhodamines; D012709:Serum Albumin; C040811:methotrexate-serum albumin; D008727:Methotrexate