Immunotoxin therapy of leptomeningeal neoplasia.
Malignant tumors of the central nervous system can result from metastatic dissemination of a variety of cancers. Percutaneous intracisternal injection of an anti-idiotype monoclonal antibody (M6) ricin immunotoxin was shown to be moderately effective in prolonging the survival of tumor bearing animals supporting the use of immunotoxins for the treatment of central nervous system neoplasia (Zovickian J and Youle R.J. J. Neurosurg 68: 767, 1988). This report describes a method that significantly improves the survival of immunotoxin treated Strain 2 guinea pigs in a syngeneic animal model of leptomeningeal neoplasia. Strain 2 guinea pigs, implanted with subarachnoid catheters, received three courses of treatment with an (M6)-intract ricin immunotoxin following intracisternal inoculation of L2C leukemia tumor cells. Animals were treated with three to four micrograms of immunotoxin in three divided doses. This was found to be less toxic and more effective than single bolus administration of immunotoxin. These results demonstrate that a permanent indwelling catheter in this animal model facilitates multiple dose delivery of immunotoxin therapy allowing the assessment of various treatment schedules and the achievement of enhanced therapeutic effect. Furthermore, these results support the continued evaluation of immunotoxins for the treatment of central nervous system neoplasia.
Walbridge
S
S
Surgical Neurology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892.
Rybak
S M
SM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001099:Arachnoid / Q000473:pathology*; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000627:therapeutic use*; D000922:Immunotoxins / Q000008:administration & dosage / Q000627:therapeutic use*; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D017254:Leukemic Infiltration / Q000401:mortality / Q000628:therapy*; D012276:Ricin / Q000008:administration & dosage / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D000922:Immunotoxins; D012276:Ricin