Long survival of patients with small cell lung cancer after adjuvant treatment with the anti-idiotypic antibody BEC2 plus Bacillus Calmette-Guérin.
Despite active therapies for small cell lung cancer (SCLC), most patients relapse and die of the disease. The present study evaluates immunization using the anti-idiotypic antibody BEC2, which mimics the ganglioside GD3 expressed on the surface of most SCLC tumors, combined with Bacillus Calmette-Guérin (BCG) as an immune adjuvant. We hypothesized that active immunization could alter the natural history of the disease. Fifteen patients who had completed standard therapy for SCLC received a series of five intradermal immunizations consisting of 2.5 mg of BEC2 plus BCG over a 10-week period. Blood was collected for serological analysis, and outcome was monitored. All patients developed anti-BEC2 antibodies, despite having received chemotherapy with or without thoracic radiation. We detected anti-GD3 antibodies in five patients, including those with the longest relapse-free survival. The median relapse-free survival for patients with extensive stage disease is 11 months and has not been reached for patients with limited stage disease (>47 months), with only one of seven patients having relapsed after a median follow-up of 47 months. Immunization of patients with SCLC after standard therapy using BEC2 plus BCG can induce anti-GD3 antibodies and is safe. The survival and relapse-free survival in this group of patients are substantially better than those observed in a prior group of similar patients. A Phase III trial is being conducted to evaluate BEC2 plus BCG as adjuvant therapy after chemotherapy and irradiation.
Grant
S C
SC
Department of Medicine, Memorial Sloan-Kettering Cancer Center and Joan and Sanford I. Weill Medical College of Cornell University, New York, New York 10021, USA.
Kris
M G
MG
Houghton
A N
AN
Chapman
P B
PB
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000009:adverse effects / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D016233:Immunotherapy, Active; D008175:Lung Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D001500:BCG Vaccine; D005732:Gangliosides; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C026226:ganglioside, GD3