IMMUNOTOXIN THERAPY OF LEPTOMENINGEAL NEOPLASIA

Malignant tumors of the central nervous system can result from metasta tic dissemination of a variety of cancers. Percutaneous intracisternal injection of an anti-idiotype monoclonal antibody (M6) ricin immunoto xin was shown to be moderately effective in prolonging the survival of tumor bearing animals supporting the use of immunotoxins for the trea tment of central nervous system neoplasia (Zovickian J and Youle R.J.J . Neurosurg 68: 767, 1988). This report describes a method that signif icantly improves the survival of immunotoxin treated Strain 2 guinea p igs in a syngeneic animal model of leptomeningeal neoplasia. Strain 2 guinea pigs, implanted with subarachnoid catheters, received three cou rses of treatment with an (M6)-intract ricin immunotoxin following int racisternal inoculation of L2C leukemia tumor cells. Animals were trea ted with three to four micrograms of immunotoxin in three divided dose s. This was found to be less toxic and more effective than single bolu s administration of immunotoxin. These results demonstrate that a perm anent indwelling catheter in this animal model facilitates multiple do se 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 immun otoxins for the treatment of central nervous system neoplasia.