Anti-ganglioside anti-idiotypic monoclonal antibody-based cancer vaccine induces apoptosis and antiangiogenic effect in a metastatic lung carcinoma.
Anti-idiotype monoclonal antibody (mAb) 1E10 was generated by immunizing BALB/c mice with an Ab1 mAb which recognizes NeuGc-containing gangliosides, sulfatides and some tumor antigens. 1E10 mAb induces therapeutic effects in a primary breast carcinoma and a melanoma model. However, the tumor immunity mechanisms have not been elucidated. Here we show that aluminum hydroxide-precipitated 1E10 mAb immunization induced anti-metastatic effect in the 3LL-D122 Lewis Lung carcinoma, a poorly immunogenic and highly metastatic model in C57BL/6 mice. The therapeutic effect was associated to the increment of T cells infiltrating metastases, the reduction of new blood vessels formation and the increase of apoptotic tumor cells in lung nodules. Interestingly, active immunization does not induce measurable antibodies to the 1E10 mAb, the NeuGc-GM3 or tumor cells, which may suggest a different mechanism which has to be elucidated. These findings may support the relevance of this target for cancer biotherapy.
Diaz
Y
Y
Experimental Immunotherapy Department, Center of Molecular Immunology, P.O. Box 16040, Havana 11600, Cuba.
Gonzalez
A
A
Lopez
A
A
Perez
R
R
Vazquez
A M
AM
Montero
E
E
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005732:Gangliosides / Q000276:immunology* / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
D000888:Antibodies, Anti-Idiotypic; D005732:Gangliosides