g(m3)-ganglioside and Carcinoma--Small-Cell

1E10 is an anti-idiotype murine monoclonal antibody (Ab2 MAb) specific to an Ab1 MAb which reacts with NeuGc-containing gangliosides, sulfatides and with antigens expressed in some human tumors. Preparations containing this Ab2 were capable to induce a strong anti-metastatic effect in tumor-bearing mice. We conducted a Phase I clinical trial to evaluate the toxicity and humoral immune response elicited by 1E10 vaccine in patients with small cell lung cancer (SCLC). Eligible patients were those who after received chemotherapy and/or radiotherapy had partial or complete response to treatment. Patients received four biweekly injections with 2 mg of aluminum hydroxide-precipitated 1E10 MAb, then other six doses at 28-day intervals, and later the patients who maintained a good performance status were reimmunized. Six patients with limited-stage disease and three with extensive-stage disease were enrolled in the study. Most of the patients who received at least four doses of 1E10 vaccine developed strong specific antibody responses against 1E10 MAb and NeuGc-GM3 ganglioside. Antibodies able to react with lung carcinoma tissue sections were detected in sera from vaccinated patients. A prolonged survival was observed in several patients treated with the anti-idiotype vaccine. No evidence of serious adverse effects was found.

Topics: Aged; Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Neoplasm; Antibody Specificity; Binding Sites, Antibody; Cancer Vaccines; Carcinoma, Small Cell; Female; G(M3) Ganglioside; Humans; Immunohistochemistry; Immunotherapy, Active; Lung Neoplasms; Male; Mice; Middle Aged; Treatment Outcome

Human lung carcinoma tissues with histological types of adenocarcinoma, squamous cell and small cell undifferentiated carcinomas were investigated for glycolipids. Carcinoma tissues, as well as normal adult and embryonic lungs contained ceramide mono-, di- and trihexosides, globoside and hematoside as major glycolipids. In addition to them, sulfatide which was identified as ceramide 3-sulfate-galactoside, was isolated in much lesser amount. The content of sulfatide was markedly increased in adenocarcinoma than that in other carcinomas and normal lung. Adenocarcinoma was also characterized by significantly lower level of total glycolipids which was largely due to the diminished contents of ceramide mono- and dihexosides, and hematoside, as compared to those in other two carcinomas. Squamous cell carcinoma had a characteristic pattern with an increment of hematoside. In small cell undifferentiated carcinoma, glycolipid contents were similar with those in squamous cell carcinoma but the relative composition of major glycolipids was markedly differed from that in other types. All the types of carcinoma examined showed marked increase of ceramide mono- and dihexosides (except for ceramide dihexoside in adenocarcinoma) compared to those in normal adult lung. Overall feature of glycolipids in embryonic lung appeared to be an intermediate between carcinomas and normal adult lung.

Topics: Adenocarcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; G(M3) Ganglioside; Globosides; Glycosphingolipids; Humans; Lung; Lung Neoplasms; Pregnancy; Sulfoglycosphingolipids; Trihexosylceramides