Inhibition of mouse SP2/0 myeloma cell growth by the B7-H4 protein vaccine
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
B7-H4 is a member of B7 family of co-inhibitory molecules andB7-H4 protein is found to be overexpressed in many humancancers and which is usually associated with poor survival. Inthis study, we developed a therapeutic vaccine made from afusion protein composed of a tetanus toxoid (TT) T-helper cellepitope and human B7-H4IgV domain (TT-rhB7-H4IgV). Weinvestigated the anti-tumor effect of the TT-rhB7-H4IgV vaccinein BALB/c mice and SP2/0 myeloma growth was significantlysuppressed in mice. The TT-rhB7-H4IgV vaccine inducedhigh-titer specific antibodies in mice. Further, the antibodiesinduced by TT-rhB7-H4IgV vaccine were capable of depletingSP2/0 cells through complement-dependent cytotoxicity (CDC)in vitro. On the other hand, the poor cellular immune responsewas irrelevant to the therapeutic efficacy. These results indicatethat the recombinant TT-rhB7-H4IgV vaccine might be a usefulcandidate of immunotherapy for the treatment of some tumorsassociated with abnormal expression of B7-H4.
Abstract
B7-H4 is a member of B7 family of co-inhibitory molecules andB7-H4 protein is found to be overexpressed in many humancancers and which is usually associated with poor survival. Inthis study, we developed a therapeutic vaccine made from afusion protein composed of a tetanus toxoid (TT) T-helper cellepitope and human B7-H4IgV domain (TT-rhB7-H4IgV). Weinvestigated the anti-tumor effect of the TT-rhB7-H4IgV vaccinein BALB/c mice and SP2/0 myeloma growth was significantlysuppressed in mice. The TT-rhB7-H4IgV vaccine inducedhigh-titer specific antibodies in mice. Further, the antibodiesinduced by TT-rhB7-H4IgV vaccine were capable of depletingSP2/0 cells through complement-dependent cytotoxicity (CDC)in vitro. On the other hand, the poor cellular immune responsewas irrelevant to the therapeutic efficacy. These results indicatethat the recombinant TT-rhB7-H4IgV vaccine might be a usefulcandidate of immunotherapy for the treatment of some tumorsassociated with abnormal expression of B7-H4.
참고문헌 (22)
- Prasad, D. V., "B7S1, a novel B7 family member that negatively regulates T cell activation", Immunity, 18, pp.863~873 (2003)
- Choi, I. H., "Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family", J. Immunol, 171, pp.4650~4654 (2003)
- Sica, G. L., "B7-H4, a molecule of the B7 family, negatively regulates T cell immunity", Immunity, 18, pp.849~861 (2003)
- Salceda, S., "The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation", Exp. Cell Res, 306, pp.128~141 (2005)
- Krambeck, A. E., "B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival", Proc. Natl. Acad. Sci. U.S.A, 103, pp.10391~10396 (2006)
- Fauci, J. M., "A review of B7-H3 and B7-H4 immune molecules and their role in ovarian cancer", Gynecol. Oncol, 127, pp.420~425 (2012)
- Simon, I., "B7-H4 is over-expressed in early-stage ovarian cancer and is independent of CA125 expression", Gynecol. Oncol, 106, pp.334~341 (2007)
- Quandt, D., "B7-h4 expression in human melanoma: its association with patients' survival and antitumor immune response", Clin. Cancer Res, 17, pp.3100~3111 (2011)
- Chen, L. J., "B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma", Cancer Immunol. Immunother, 60, pp.1047~1055 (2011)
- Sun, S. Q., "Enhanced T cell immunity by B7-H4 downregulation in nonsmall-cell lung cancer cell lines", J. Int. Med. Res, 40, pp.497~506 (2012)
- Kryczek, I., "B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma", J. Exp. Med, 203, pp.871~881 (2006)
- Dalum, I., "Therapeutic antibodies elicited by immunization against TNF-alpha", Nat. Biotechnol, 17, pp.666~669 (1999)
- Dalum, I., "Induction of cross-reactive antibodies against a self protein by immunization with a modified self protein containing a foreign T helper epitope", Mol. Immunol, 34, pp.1113~1120 (1997)
- Valmori, D., "Use of human universally antigenic tetanus toxin T cell epitopes as carriers for human vaccination", J. Immunol, 149, pp.717~721 (1992)
- Yu, Z., "Peptide-antibody conjugates for tumour therapy: a MHC-class-II-restricted tetanus toxin peptide coupled to an anti-Ig light chain antibody can induce cytotoxic lysis of a human B-cell lymphoma by specific CD4 T cells", Int. J. Cancer, 56, pp.244~248 (1994)
- Zhang, C., "B7-H1 protein vaccine induces protective and therapeutic antitumor responses in SP2", 0 myeloma-bearing mice, 2013, pp.30, 2442~2448
- Suh, W. K., "Generation and characterization of B7-H4", B7S1, Mol. Cell Biol, pp.2006, 26[DOI]
- Hansen, J. D., "The B7 family of immunoregulatory receptors: a comparative and evolutionary perspective", Mol. Immunol, 46, pp.457~472 (2009)
- Zhang, C., "Anti-tumor immunotherapy by blockade of the PD-1", PD-L1 pathway with recombinant human PD-1-IgV, 2008, pp.10, 711~719
- Kryczek, I., "Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma", Cancer Res, 67, pp.8900~8905 (2007)
- Lin, C. C., "Therapeutic HER2", Neu DNA vaccine inhibits mouse tumor naturally overexpressing endogenous neu, 2004, pp.10, 290~301
- Renard, V., "HER-2 DNA and protein vaccines containing potent Th cell epitopes induce distinct protective and therapeutic antitumor responses in HER-2 transgenic mice", J. Immunol, 171, pp.1588~1595 (2003)