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[Cancer Research 65, 1089-1096, February 1, 2005]
© 2005 American Association for Cancer Research

Immunology

Blockade of B7-H1 and PD-1 by Monoclonal Antibodies Potentiates Cancer Therapeutic Immunity

Fumiya Hirano1, Katsumi Kaneko1, Hideto Tamura1, Haidong Dong1, Shengdian Wang1,2, Masao Ichikawa1,2, Cecilia Rietz1,2, Dallas B. Flies1,2, Julie S. Lau1, Gefeng Zhu1,2, Koji Tamada1,2 and Lieping Chen1,2

1 Department of Immunology, Mayo Clinic, Rochester, Minnesota and 2 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland

Requests for reprints: Lieping Chen, Johns Hopkins Medical Institutions, 600 North Wolfe Street, Jefferson Street, Building 1-121, Baltimore, MD 21287. Phone: 410-502-0957; Fax: 410-502-0961l; E-mail: lchen42{at}jhmi.edu.

Contemporary approaches for vaccination and immunotherapy are often capable of eliciting strong T-cell responses against tumor antigens. However, such responses are not parallel to clinical tumor regression. The development of evasion mechanisms within tumor microenvironment may be responsible for poor therapeutic responses. We report here that constitutive or inducible expression of B7-H1, a B7 family molecule widely expressed by cancers, confers resistance to therapeutic anti-CD137 antibody in mice with established tumors. The resistance is accompanied with failure of antigen-specific CD8+ CTLs to destroy tumor cells without impairment of CTL function. Blockade of B7-H1 or PD-1 by specific monoclonal antibodies could reverse this resistance and profoundly enhance therapeutic efficacy. Our findings support that B7-H1/PD-1 forms a molecular shield to prevent destruction by CTLs and implicate new approaches for immunotherapy of human cancers.

Key Words: PD-1 • immune surveillance • lymphocyte activation




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