Introduction of 65 kDa antigen of Mycobacterium tuberculosis to cancer cells enhances anti-tumor effect of BCG therapy.

Abstract

Bacillus Calmette Guerin (BCG) immunotherapy has anti-tumorigenic effects against bladder cancer. To improve the efficacy of BCG therapy, we introduced the gene encoding the 65 kDa heat shock protein (hsp) of Mycobacterium tuberculosis into a mouse malignant melanoma cell line (B16). An expression vector harboring the 65 kDa antigen gene was transfected into B16 using Lipofectamine, then expression of the antigen was confirmed by RT-PCR and Western blotting. Several cell lines expressing 65 kDa antigen were established (B16/65 kDa). We also established a control cell line transfected with the vector alone (B16/con). All cell lines (B16, B16/con, B16/65 kDa) were injected intraperitoneally into syngeneic mice with or without BCG prior immunization and the development of tumor ascites was examined. To analyze the mechanism of the anti-tumor effect, CD4 T cells or CD8 T cells were depleted in vivo by administering the corresponding monoclonal antibody. B16/65k Da expressed the 65 kDa hsp of M. tuberculosis. The tumor growth of B16/65 kDa was slightly retarded in naive mice, but significantly inhibited by BCG. The anti-tumor effect was totally abrogated in mice deficient in CD4 T cells, suggesting that CD4 T cells are involved in this process. The 65 kDa hsp of M. tuberculosis was expressed after gene transduction in a malignant melanoma cell line and significantly enhanced the anti-tumor effect of BCG immunotherapy. CD4 T cells play an important role in this anti-tumor effect.

• Authors: Isao Hara, Noriyuki Sato, Hideaki Miyake, Mototsugu Muramaki, Satoko Hikosaka, Sadao Kamidono
• Journal: Microbiology and immunology (Microbiol Immunol) Vol. 48 Issue 4 Pg. 289-95 ( 2004) ISSN: 0385-5600 [Print] Australia
• PMID: 15107539 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BCG Vaccine
• Bacterial Proteins
• Chaperonin 60
• heat-shock protein 65, Mycobacterium
• Chaperonins

Topics

• Animals
• BCG Vaccine (administration & dosage, immunology)
• Bacterial Proteins (genetics, immunology, metabolism)
• Cell Line, Tumor
• Chaperonin 60
• Chaperonins (genetics, immunology, metabolism)
• Immunotherapy (methods)
• Injections, Intraperitoneal
• Melanoma (pathology, prevention & control)
• Mice
• Mice, Inbred C57BL
• Mycobacterium tuberculosis (immunology)
• Neoplasm Transplantation (pathology)
• Neoplasms, Experimental (physiopathology, prevention & control)
• Transfection
• Transplantation, Isogeneic (pathology)