Anti-tumor activity and immunogenicity of a mutated staphylococcal enterotoxin C2.

Abstract

In this study, a novel SEC2 mutant with lower toxic activity, named 2M-118 (H118A/T20L/G22E), was engineered by site-directed mutagenesis of structural domains that are responsible for MHC class II molecule binding and TCR binding, respectively. Stimulating activity on murine splenocytes, anti-tumor effect and immunogenicity of 2M-118 were investigated in BALB/c mice. 2M-118 not only remained splenocyte stimulation activity, but also effectively inhibited the growth of S180 sarcoma in the BALB/c mice. Even though antibodies to 2M-118 could be induced after repeated administration, the action of 2M-118 was hardly neutralized or cross neutralized. Like other superantigens, immunosuppression could happen when 2M-118 was given at a greater dose. In conclusion, 2M-118 is a promising anti-tumor drug candidate for its acceptable toxicity and satisfying anti-tumour efficacy.

• Authors: J Zhang, Y M Cai, M K Xu, Z H Song, C Y Li, H R Wang, H H Dai, Z P Zhang, C X Liu
• Journal: Die Pharmazie (Pharmazie) Vol. 68 Issue 5 Pg. 359-64 (May 2013) ISSN: 0031-7144 [Print] Germany
• PMID: 23802434 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Enterotoxins
• Receptors, Antigen, T-Cell
• enterotoxin C, staphylococcal

Topics

• Animals
• Antineoplastic Agents
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Enterotoxins (immunology, pharmacology, toxicity)
• Enzyme-Linked Immunosorbent Assay
• Genes, MHC Class II (genetics)
• Humans
• Lymphocytes (drug effects)
• Mice
• Mice, Inbred BALB C
• Mutagenesis, Site-Directed
• Plasmids (genetics)
• Receptors, Antigen, T-Cell (drug effects, metabolism)
• Spleen (cytology, drug effects)
• Staphylococcus aureus (chemistry, genetics)