Immune responses in breast cancer patients immunized with an anti-idiotype antibody mimicking NeuGc-containing gangliosides

Characterization of the Antibody Response against NeuGcGM3 Ganglioside Elicited in Non-Small Cell Lung Cancer Patients Immunized with an Anti-Idiotype Antibody

“…From these latter studies, high titer Ab responses to NeuGc-containing gangliosides were measured in the sera of cancer patients. A fraction of non-suppressible anti-NeuGc-containing ganglioside Abs was demonstrated through adsorption of these sera with 1E10 mAb, suggesting that 1E10 Id vaccination might enhance antitumor natural immune response (20,26). Furthermore, NeuGcGM3-specific IFN-␥-secreting cells were measured by ELISPOT from PBMC of 1E10-vaccinated breast cancer patients (27).…”

“…This Ab2, named 1E10 (17), was generated from the immunization of BALB/c mice with P3, an idiotypic Ab (Ab1) that recognizes NeuGc-containing gangliosides, sulfated glycolipids, and Ags present in different human tumors including those from the lung, and which contains a regulatory Id according to Bona's concept (18 -24). Preparations containing 1E10 mAb were able to induce antitumor effects against lung metastases in murine models, and phase I clinical trials have proven the safety and immunogenicity of 1E10 Id vaccination in melanoma and breast cancer patients (20,25,26). From these latter studies, high titer Ab responses to NeuGc-containing gangliosides were measured in the sera of cancer patients.…”

Lonely killers

“…[58][59][60][61]63 A positive correlation between the development of such antibodies and patient survival was found. 63 Despite the lack of direct cytotoxicity by P3 mAb, 66 the antibodies generated by the anti-idiotypic vaccine were able to directly kill GM3(Neu5Gc)-expressing cells.…”

“…GM3(Neu5Gc) is a ganglioside whose expression has been detected in some human tumors, including breast and melanoma. 53,55,56 Several therapeutic strategies have been developed against this target, 14 e.g., vaccines (ganglioside-based 57 and antiidiotypic [58][59][60][61][62][63] ) and mAbs. 55 14F7 mAb is specific for this ganglioside and unable to bind its N-acetylated (Neu5Ac) counterpart.…”

Session 3: Cancer – III

“…: GD2 in neuroblastomas, GD3 in melanomas, GM3 and GD3 on breast carcinomas), normal cells show negative or faint reaction with relevant anti ganglioside antibodies. Gangliosides may serve as useful target antigen for antibody mediated immunotherapy (11,12). As it is diffi-cult to get human anti-GD3 antibodies because of their little immunogenicity, our novel way to develop antibody fragments with this specificity on breast carcinomas seems to be of great interest.…”