A PHASE I II STUDY OF THE INTRALESIONAL INJECTION OF RICIN-MONOCLONALANTIBODY CONJUGATES IN PATIENTS WITH HEPATIC METASTASES/

A phase I/II study of the intralesional administration of ricin-labell ed monoclonal antibodies was conducted in patients with hepatic metast ases of gastrointestinal origin. The anti-carcinoembryonic antigen (CE A) antibody I-1 was conjugated to blocked ricin via a disulphide bridg e. After a test dose of antibody, patients were injected with ricin-an tibody conjugates under computed tomography (CT) guidance on two occas ions 1 week apart. Patients with stable or responding disease would re ceive a third course. The dose of ricin relative to surface area was i ncreased in a predefined manner in cohorts of 3 patients. A total of 2 7 patients with hepatic metastases were entered into this study. All p atients had metastatic colorectal cancer (26 patients) or adenocarcino ma of unknown primary with elevated CEA levels (1 patient). The presen ce of malignancy was documented cytologically in 9 of 11 patients test ed. Minor responses were seen in 7 patients. However, no major objecti ve responses or changes in the growth rate of injected lesions were ob served. Toxicity was generally mild, the most common being hepatic cap sular pain 24-48 h after each injection. 6 patients experienced rigors . One patient had anaphylaxis. Human anti-mouse and anti-ricin antibod y responses were observed. Although substantial amounts of ricin conju gated to monoclonal antibodies were delivered into single lesions, thi s therapeutic approach was unsuccessful. Future studies of ricin-label led antibodies should incorporate the systemic administration of immun oconjugates.