A Mouse IgG₁Monoclonal Antibody Specific forN-Glycolyl GM3 Ganglioside Recognized Breast and Melanoma Tumors

Abstract

14F7 murine monoclonal antibody (MAb) is an IgG1 immunoglobulin that is generated by immunizing Balb/c mice with GM3(NeuGc) ganglioside hydrophobically conjugated with human very-low-density lipoproteins and in the presence of Freund's adjuvants. 14F7 MAb binds specifically to GM3(NeuGc), whereas neither N-glycolyl or N-acetyl gangliosides, nor a sulfated glycolipid, are recognized as assessed by enzyme-linked immunosorbent assay or immunostaining on thin layer chromatograms. Immunohistochemical studies in fresh tumor tissues showed that 14F7 MAb strongly recognized in antigen expressed in human breast and melanoma tumors.

An Anti-Idiotype Vaccine Elicits a Specific Response to N-Glycolyl Sialic Acid Residues of Glycoconjugates in Melanoma Patients

“…Titer was defined as the highest serum dilution giving absorbance values Ն0.2 and being at least three times the value corresponding to the preimmune serum at the same dilution. Different murine mAbs were used in the study as controls: ior-CEA1 (IgG1, , anti-carcinoembryonic Ag), ior-C5 (IgG1, ) against a glycoprotein expressed on human colorectal cells, and 14F7 (IgG1, ) anti-NeuGc-GM 3 (27)(28)(29).…”

Lonely killers

“…64 14F7 mAb was able to recognize breast and melanoma tumors by immunohistochemistry, 53 and also breast cancer by radioimmunoscintigraphy, in a Phase 1/2 diagnostic clinical study. 55 14F7 mAb displayed anti-tumor properties in vivo against a GM3(Neu5Gc)-expressing murine myeloma.…”

“…51 The 84 mAb induced membrane pores in treated cells. 52 Another well characterized antibody exhibiting this effect on plasma membrane is 14F7 mAb, 53 which targets the tumor-associated GM3(Neu5Gc). 14 14F7 mAb.…”

“…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.…”

“…55 14F7 mAb is specific for this ganglioside and unable to bind its N-acetylated (Neu5Ac) counterpart. 53 Its exquisite specificity for GM3(Neu5Gc), which differs from …”