Abstract
Tumor cells engineered to express immunogenes have been used for cancer vaccines to induce antitumor immunity and to study the antitumor immune mechanisms derived from immunogene expression. In this chapter, we describe the design and methods for cloning a cDNA gene coding for the mouse CD40L molecule and for construction of the expression vector pcDNA-CD40L, as well as the methods for generation of engineered myeloma cells J558/CD40L expressing CD40 ligand. We also demonstrate that the engineered J558/CD40L tumor cells lose their tumori- genicity in syngeneic mice, and that the inoculation of J558/CD40L tumor cells further leads to protective immunity against wild-type J558 tumors.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Blankenstein T., Qin Z., Uberla K., et al. (1991) Tumor suppression after tumor cell-targeted tumor necrosis factor gene transfer. J. Exp. Med. 173, 1047ā1052.
Qi Y., Chen Y., and Xiang J. (1996) Mouse myeloma cell line secreting bifunc-tional fusion protein RM4/IFN elicits antitumor CD8 MHC class I-restricted T cells that are cytolytic in vitro and tumoricidal in vivo. J. Interferon Cytokine Res. 16, 771ā776.
Koshita Y., Lu Y., Fujii S., et al. (1995) Efficiency of TNF-Ī± gene-transduced tumor cells in treatment of established in vivo tumor. Int. J. Cancer 63, 130ā135.
Colombo M., Ferrari G., Stoppacciaro A., et al. (1991) Granulocyte colony-stimulating factor gene transfer suppresses tumorigenicity of a murine adenocar-cinoma in vivo. J. Exp. Med. 173, 889ā897.
Allione A., Consalvo M., Manni P., Cavallo F., Giovarelli M., and Forni G. (1994) Immunizing and curative potential of replicating and nonreplicating murine mammary adenocarcinoma cells engineered with IL-2, IL-4, IL-6, IL-7, IL-10, TNF, GMCSF and IFN gene or admixed with conventional adjuvants. Cancer Res. 54, 6022ā6026.
Linsley P. and Ledbetter J. (1993) The role of CD28 receptor during T cell responses to antigen. Annu. Rev. Immunol. 11, 191ā212.
Schwartz R. (1992) Costimulation of T lymphocytes: the role of CD28, CTLA-4 and 41BBL in IL-2 production and immunotherapy. Cell 71, 1065ā1072.
Hathcock K., Laszlo C., Pucillo C., Linsley P., and Hodes R. (1994) Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function. J. Exp. Med. 180, 631ā640.
Cayeux S., Beck C., Dorken B., and Blankenstein T. (1996) Coexpression of IL-4 and B7-1 in murine tumor cells leads to improved tumor rejection and vaccine effect compared to single gene transfectants and a classical adjuvant. Hum. Gene Ther. 7, 525ā529.
Cayeux S., Richter G., Noffz G., Dorken B., and Blankenstein T. (1997) Influence of gene-modified (IL-7, IL-7 and B7-1) tumor cell vaccines on tumor antigen presentation. J. Immunol. 158, 2834ā2841.
Wu T. C., Huang A., Jaffee E., Levitsky H., and Pardoll D. (1995) A reassessment of the role of B7-1 expression in tumor rejection. J. Exp. Med. 182, 1415ā1421.
Restifo N. P., Esquivel F., Asher A. L., et al. (1991) Defective presentation of endogenous antigens by a murine sarcoma: implications for the failure of an anti-tumor response. J. Immunol. 147, 1453ā1459.
Van Essen D., Kikutani H., and Gray D. (1995) CD40 preferentially costimu-lates activation of T cell in the development of helper function. Nature 378, 620ā622.
Blotta M. H., Marshall J. D., DeKruyff R., and Umetsu D. T. (1996) Crosslinking of the CD40 ligand on human CD4+ T lymphocytes generates a co-stimulatory signal that up-regulates IL-4 synthesis. J. Immunol. 156, 3133ā3142.
Grewal I. S., Xu J., and Flavell R. A. (1995) Impairment of antigen specific T cell priming in mice lacking CD40 ligand. Nature 378, 617ā623.
Roy M., Waldschmidt T., Aruffo A., Ledbetter J. A., and Noelle R. J. (1993) The regulation of the expression of gp39, the CD40 ligand on normal and cloned CD4 T cells. J. Immunol. 151, 497ā2510.
Grewal I. and Flavell R. (1998) CD40 and CD154 in cell-mediated immunity. Annu. Rev. Immunol. 16, 111ā135.
Smith C., Farrah T., and Goodwin R. (1994) The TNF receptor superfamily of cellular and viral proteins: activation, costimulation and death. Cell 76, 959ā962.
Foy T. M., Shepherd D. M., Durie F. H., Aruffo A., Ledbetter J. A., and Noelle R. J. (1993) In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. II. Prolonged suppression of the humoral immune response by an antibody to the ligand for CD40, gp39. J. Exp. Med. 178, 1567ā1575.
Schoenberger S. P., Toes R. E., van der Voort E. L., Offringa R., and Melief C. J. (1998) T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393, 480ā483.
Caux C., Massacrier C., and Vanbervliet B. (1994) Activation of human dendritic cells through CD40 cross-linking. J. Exp. Med. 180, 1263ā1272.
Cella M., Scheidegger D., Palmer-Lehmann K., Lane P., Lanzavecchia A., and Alber G. (1996) Ligation of CD40 on dendritic cells triggers production of high levels of IL-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J. Exp. Med. 184, 747ā752.
Koch F., Stanzl U., Jennewein P., et al. (1996) High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10. J. Exp. Med. 184, 741ā746.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
Ā© 2005 Humana Press Inc.
About this protocol
Cite this protocol
Hao, S., Chan, T., Xiang, J. (2005). Genetically Engineered Myeloma Cell Vaccine. In: Brown, R.D., Ho, P.J. (eds) Multiple Myeloma. Methods in Molecular Medicineā¢, vol 113. Humana Press. https://doi.org/10.1385/1-59259-916-8:235
Download citation
DOI: https://doi.org/10.1385/1-59259-916-8:235
Publisher Name: Humana Press
Print ISBN: 978-1-58829-392-3
Online ISBN: 978-1-59259-916-5
eBook Packages: Springer Protocols