Co-expression of P1A35-43/beta2m fusion protein and co-stimulatory molecule CD80 elicits effective anti-tumor immunity in the P815 mouse mastocytoma tumor model.

Abstract

A strong CTL response is dependent upon a high level of expression of specific class I major histocompatibility complex (MHC)/peptide complexes at the cell surface. An epitope-linked beta2-microglobulin (beta2m) molecule could provide a simple and more efficient means to enhance the formation of defined MHC/peptide complexes. However, the ability of an epitope-linked beta2m molecule to elicit primary CTL responses in vivo is still unknown. In this study, we modified the P1A tumor cell vaccine by addition of the tumor-associated epitope (TAE)-linked beta2m molecule and co-stimulatory molecule CD80 to improve the efficiency in the application of the vaccine. A eukaryotic co-expression vector consisting of the P1A35-43-linked beta2m molecule and the murine CD80 gene was constructed. P815 cell lines stably expressing P1A35-43-linked beta2m molecule and/or CD80 were established after transfection, by selection under G418. Administration of these inactivated tumor cell vaccines allowed the TAE-specific CD8+ T cell responses to be examined in vivo. Our results indicate that immunization with P815 cells expressing both the P1A35-43-linked beta2m molecule and the murine CD80 gene elicited a significantly stronger antitumor immune response than the single-modified tumor cell vaccines (expressing either P1A35-43-linked beta2m or CD80 alone). These findings support the feasibility and effectiveness of developing a dual-modified tumor cell vaccine consisting of the epitope-linked beta2m molecule and a co-stimulatory molecule.

• Authors: Xingqian Zhang, Wenhan Mei, Leilei Zhang, Hai Yu, Xiaoping Zhao, Xianqun Fan, Guanxiang Qian, Shengfang Ge
• Journal: Oncology reports (Oncol Rep) Vol. 22 Issue 5 Pg. 1213-20 (Nov 2009) ISSN: 1021-335X [Print] Greece
• PMID: 19787242 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• B7-1 Antigen
• Cancer Vaccines
• Recombinant Fusion Proteins
• beta 2-Microglobulin
• tumor rejection antigen P815A, mouse
• Interferon-gamma

Topics

• Animals
• Antigens, Neoplasm (genetics, immunology)
• B7-1 Antigen (genetics, immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (therapeutic use)
• Feasibility Studies
• Female
• Immunization
• Interferon-gamma
• Mastocytoma (genetics, immunology, therapy)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Recombinant Fusion Proteins (genetics, immunology)
• Spleen (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• beta 2-Microglobulin (genetics, immunology)