IBH1 Antibody

Mechanism of Action

IDH1 antibodies target the cytoplasmic enzyme isocitrate dehydrogenase 1, which catalyzes the conversion of isocitrate to α-ketoglutarate. Mutations in IDH1 (e.g., R132H) alter enzymatic activity, producing an oncometabolite (2-hydroxyglutarate) that drives tumorigenesis .

Key Features of IDH1 Antibodies:

Clinical Applications

IDH1 antibodies are pivotal in neuropathology for diagnosing gliomas.

Diagnostic Use in Gliomas

• Immunohistochemistry (IHC):

  • MRQ-67 and IMab-1: Specifically detect R132H mutations in diffuse astrocytomas, oligodendrogliomas, and secondary glioblastomas. No staining in primary glioblastomas or IDH1-wild-type tumors .

  • H09 vs. MRQ-67: MRQ-67 shows higher affinity and reduced background staining compared to H09, improving diagnostic accuracy .

Western Blot (WB) Validation

• MAB7049: Detects a 46–47 kDa band in human, mouse, and rat lysates. Knockout validation confirms specificity .

• PB9601: Identifies IDH1 in HepG2, A549, and HepG2 cells; no signal in IDH1 knockout models .

Specificity and Sensitivity

• IMab-1: Recognizes only R132H and not other mutants (R132C, R132G, R132L, R132S) or wild-type IDH1 .

• MRQ-67: DNA sequencing confirmed R132H mutations in all IHC-positive gliomas (5/5 cases) and none in negatives (0/13) .

Therapeutic Implications

While primarily diagnostic, IDH1 antibodies may inform therapeutic strategies targeting mutant IDH1 enzymes. For example, inhibitors of 2-hydroxyglutarate production are under investigation in glioma trials .

Challenges and Future Directions

• Cross-reactivity: Early antibodies like H09 show background staining, necessitating improved clones (e.g., MRQ-67) .

• Therapeutic Antibodies: Potential for engineered antibodies to neutralize mutant IDH1 activity or deliver targeted therapies .