Cross-reacting material 197 (CRM197) (CRM197)

Cross-reacting material 197 (CRM197) is a genetically detoxified mutant of the diphtheria toxin, produced by Corynebacterium diphtheriae, featuring a single amino acid substitution (Gly52Glu) that abolishes its ADP-ribosyltransferase activity while maintaining its immunological properties and receptor-binding capability (Giannini et al., 1984). It is the most widely used carrier protein in conjugate vaccines, such as those targeting Streptococcus pneumoniae and Neisseria meningitidis, where it functions by converting T-cell independent polysaccharide antigens into T-cell dependent ones to elicit a robust and lasting immune response (Bröker et al., 2011). Beyond vaccinology, CRM197 serves as a specific ligand for the heparin-binding EGF-like growth factor (HB-EGF) receptor, which is frequently overexpressed in various malignancies, including ovarian and breast cancers (Miyamoto et al., 2004). This binding allows CRM197 to act as a therapeutic agent by inhibiting HB-EGF-mediated signaling or as a targeting moiety for the delivery of cytotoxic payloads to tumor cells. Furthermore, its ability to undergo receptor-mediated transcytosis across the blood-brain barrier has positioned it as a promising candidate for central nervous system drug delivery systems (Pardridge, 2007).

Other names

CRM-197Diphtheria toxin CRM197Nontoxic mutant of diphtheria toxinGly52Glu diphtheria toxin mutantDiphtheria toxoid CRM197

In the context of conjugate vaccines, CRM197 acts as a carrier protein that provides essential T-cell epitopes; once the conjugate is internalized by B-cells, CRM197-derived peptides are presented via MHC class II molecules to T-helper cells, which then provide the necessary signals for B-cell maturation and memory formation (Bröker et al., 2011). In its role as a therapeutic ligand, CRM197 binds to the heparin-binding EGF-like growth factor (HB-EGF) with high affinity, preventing HB-EGF from activating the epidermal growth factor receptor (EGFR) and thereby inhibiting downstream oncogenic signaling pathways such as PI3K/Akt and MAPK/ERK (Miyamoto et al., 2004).