Diphtheria toxin CRM197 mutant (CRM197)

Diphtheria toxin CRM197 mutant is a non-toxic form of the diphtheria toxin produced by Corynebacterium diphtheriae, resulting from a single amino acid substitution (Gly52Glu) in the A-subunit (Giannini et al., 1984, Nucleic Acids Res.). This mutation eliminates the ADP-ribosyltransferase activity responsible for the toxin's lethality while preserving its structural integrity and immunogenic properties (Rappuoli, 1997, Vaccine). It is most prominently used as a carrier protein in conjugate vaccines, such as those against Streptococcus pneumoniae and Neisseria meningitidis, where it facilitates a T-cell dependent immune response to polysaccharide antigens (Pichichero, 2013, Hum Vaccin Immunother). Additionally, CRM197 functions as a specific ligand for the heparin-binding EGF-like growth factor (HB-EGF) receptor, which is often overexpressed in various cancers (Miyamoto et al., 2004, Cancer Res). By binding to HB-EGF, CRM197 can inhibit tumor cell proliferation and is being investigated as a targeted therapy or delivery system for oncology applications (Yagi et al., 2009, Cancer Sci). Its extensive clinical use in pediatric and adult vaccines has established a well-characterized safety and efficacy profile (Broker et al., 2011, Vaccine).

Other names

Cross-reacting material 197CRM-197Non-toxic diphtheria toxin mutantGly52Glu diphtheria toxin

Acts as a carrier protein to convert T-cell independent polysaccharide antigens into T-cell dependent antigens, thereby inducing a robust immune response; also acts as a competitive inhibitor of HB-EGF receptor binding to suppress tumor growth.