4-1BB ligand enhances tumor-specific immunity of poxvirus vaccines.

Vaccine
Chie Kudo-SaitoHoward L Kaufman

Abstract

Recombinant poxvirus vaccines have been explored as tumor vaccines. The immunogenicity of these vaccines can be enhanced by co-expressing costimulatory molecules and tumor-associated antigens. While the B7-CD28 interaction has been most comprehensively investigated, other costimulatory molecules utilize different signaling pathways and might provide further cooperation in T cell priming and survival. 4-1BB (CD137) is a TNF family member and is critical for activation and long-term maintenance of primed T cells. This study was conducted to determine if a poxvirus expressing the ligand for 4-1BB (4-1BBL) could further improve the immune and therapeutic responses of a previously reported poxvirus vaccine expressing a triad of costimulatory molecules (B7.1, ICAM-1, and LFA-3). A recombinant vaccinia virus expressing 4-1BBL was generated and characterized in an in vitro infection system. This vaccine was then used alone or in combination with a vaccinia virus expressing CEA, B7.1, ICAM-1, and LFA-3 in CEA-transgenic mice bearing established MC38 tumors. Tumor growth and immune responses against CEA and other tumor-associated antigens were determined. The level of anti-apoptotic proteins in responding T cells was determined by flow c...Continue Reading

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Citations

Jan 5, 2010·Immunotherapy·Angela D PardeeWalter J Storkus
Feb 9, 2012·Clinical & Developmental Immunology·Kuang YoulinZhu Hengchen
Nov 28, 2007·Journal of Translational Medicine·Howard L KaufmanJohn Marshall
Aug 19, 2007·Immunologic Research·Matthew A Fischer, Christopher C Norbury
Jun 15, 2007·International Reviews of Immunology·Robert C Ward, Howard L Kaufman
Jun 25, 2015·Frontiers in Oncology·Todd Bartkowiak, Michael A Curran
Jan 19, 2011·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Xiaodong WengHao Shen
Feb 28, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Han XiaoZuo-Hua Feng

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