Immunotoxin therapy of small-cell lung cancer. N901-blocked ricin for relapsed small-cell lung cancer.

Abstract

Despite its initial chemosensitivity, small-cell lung cancer (SCLC) is rarely cured with chemotherapy alone, and fewer than 5% of patients are alive at 5 years. Immunotoxin therapy appears to offer promise in treating the minimal residual disease that remains after induction chemotherapy. We have studied N901-bR in patients with relapsed SCLS. N901-bR consists of the N901 monoclonal antibody (MoAb) and blocked ricin, an altered ricin molecule in which the galactose binding sites of the ricin B-chain which mediate nonspecific binding of the toxin are blocked through the covalent binding of ligands. N901 is an anti-NCAM (CD56) MoAb which binds to SCLC tumors and cell lines, cardiac muscle, natural killer (NK) cells, and peripheral nerve. N901-bR showed a 2.7 log greater in vitro cytotoxicity to the CD56-positive cell line SE-2 than to the antigen-negative Namalwa cell line. Nineteen patients with relapsed antigen-negative Namalwa cell line. Nineteen patients with relapsed and/or refractory SCLC have been entered into a phase I study at doses ranging from 5 to 40 micrograms/kg/day given as a 7-day continuous infusion. The dose-limiting toxicity is capillary leak syndrome observed in two thirds of the patients treated at 40 micrograms/kg/day. One patient at the maximum tolerated dose, 30 micrograms/kg/day x 7 days, has achieved a partial response to N901-bR. No patient has developed clinically significant peripheral or central neuropathy. We plan to begin a phase II study of N901-bR following induction chemotherapy in patients with SCLC.