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.
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.
Zhang
Xingqian
X
Department of Biochemistry and Molecular Biology, Research Center for Human Gene Therapy, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, PR China.
Mei
Wenhan
W
Zhang
Leilei
L
Yu
Hai
H
Zhao
Xiaoping
X
Fan
Xianqun
X
Qian
Guanxiang
G
Ge
Shengfang
S
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D007114:Immunization; D007371:Interferon-gamma; D034801:Mastocytoma / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology*
D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D019496:Cancer Vaccines; D011993:Recombinant Fusion Proteins; D001613:beta 2-Microglobulin; C076546:tumor rejection antigen P815A, mouse; D007371:Interferon-gamma