Immunotoxin therapy of small-cell lung cancer. N901-blocked ricin for relapsed small-cell lung cancer.
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.
Division of Clinical Oncology, Dana-Farber Cancer Institute, Boston.
T J
TJ
Lynch
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000954:Antigens, Surface; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000628:therapy*; D003131:Combined Modality Therapy; D006801:Humans; D018796:Immunoconjugates; D007167:Immunotherapy; D000922:Immunotoxins / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D012276:Ricin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D017211:Treatment Failure
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018796:Immunoconjugates; D000922:Immunotoxins; C080540:N901 MoAb-blocked ricin conjugate; D012276:Ricin