Improved tumor-specific immunotoxins in the treatment of CNS and leptomeningeal neoplasia.
A novel antibody-toxin conjugate has been developed for use in cancer therapy. This report demonstrates that this new reagent selectively kills glioblastoma- and medulloblastoma-derived cell lines, medulloblastoma cells in primary culture, and cell lines derived from tumors commonly metastatic to the cerebrospinal fluid (CSF). Efficient killing of human tumor cells occurred at concentrations between 3.9 X 10(-13) M and 1.1 X 10(-10) M, whereas guinea pigs and rhesus monkeys tolerated intrathecal levels of 2 X 10(-9) M. Cerebrospinal fluid from normal humans and from brain-tumor patients does not inhibit the in vitro efficacy of this reagent. The wide therapeutic window, extreme potency, and general applicability of this antibody-toxin conjugate against CSF-borne primary or metastatic tumors warrants clinical trials.
Surgical Neurology Branch, National Institute of Neurological Communicative Diseases and Stroke, Bethesda, Maryland.
V G
VG
Johnson
C
C
Wrobel
D
D
Wilson
J
J
Zovickian
L
L
Greenfield
E H
EH
Oldfield
R
R
Youle
D000368:Aged; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000502:physiology; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D002648:Child; D004167:Diphtheria Toxin / Q000276:immunology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D008253:Macaca mulatta; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy*; D008875:Middle Aged; D009423:Nervous System Neoplasms / Q000188:drug therapy*; D011990:Receptors, Transferrin / Q000276:immunology / Q000502:physiology; D012276:Ricin; D014168:Transferrin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000906:Antibodies; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; C058384:CRM 107; D004167:Diphtheria Toxin; D000922:Immunotoxins; D011990:Receptors, Transferrin; D014168:Transferrin; D012276:Ricin