Anti-ganglioside anti-idiotypic monoclonal antibody-based cancer vaccine induces apoptosis and antiangiogenic effect in a metastatic lung carcinoma |
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Authors: | Y Diaz A Gonzalez A Lopez R Perez A M Vazquez E Montero |
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Institution: | (1) Experimental Immunotherapy Department, Center of Molecular Immunology, P.O. Box 16040, Havana, 11600, Cuba;(2) Research and Development, Center of Molecular Immunology, Havana, Cuba;(3) Antibody Engineering Department, Center of Molecular Immunology, P.O. Box 16040, Havana, 11600, Cuba |
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Abstract: | 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. |
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Keywords: | Cancer vaccine Lung carcinoma metastases Anti-idiotype monoclonal antibody NeuGc-containing ganglioside Apoptosis Angiogenesis |
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