Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity

Fumiya Hirano, Katsumi Kaneko, Hideto Tamura, Haidong M Dong, Shengdian Wang, Masao Ichikawa, Cecilia Rietz, Dallas B. Flies, Julie S. Lau, Gefeng Zhu, Koji Tamada, Lieping Chen

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1089-1096
Number of pages8
JournalCancer Research
Volume65
Issue number3
StatePublished - Feb 1 2005

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Immunity
Monoclonal Antibodies
Neoplasms
Immunotherapy
B7 Antigens
CD8 Antigens
Therapeutics
Tumor Microenvironment
Neoplasm Antigens
Anti-Idiotypic Antibodies
Vaccination
T-Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hirano, F., Kaneko, K., Tamura, H., Dong, H. M., Wang, S., Ichikawa, M., ... Chen, L. (2005). Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Research, 65(3), 1089-1096.

Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. / Hirano, Fumiya; Kaneko, Katsumi; Tamura, Hideto; Dong, Haidong M; Wang, Shengdian; Ichikawa, Masao; Rietz, Cecilia; Flies, Dallas B.; Lau, Julie S.; Zhu, Gefeng; Tamada, Koji; Chen, Lieping.

In: Cancer Research, Vol. 65, No. 3, 01.02.2005, p. 1089-1096.

Research output: Contribution to journalArticle

Hirano, F, Kaneko, K, Tamura, H, Dong, HM, Wang, S, Ichikawa, M, Rietz, C, Flies, DB, Lau, JS, Zhu, G, Tamada, K & Chen, L 2005, 'Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity', Cancer Research, vol. 65, no. 3, pp. 1089-1096.
Hirano F, Kaneko K, Tamura H, Dong HM, Wang S, Ichikawa M et al. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Research. 2005 Feb 1;65(3):1089-1096.
Hirano, Fumiya ; Kaneko, Katsumi ; Tamura, Hideto ; Dong, Haidong M ; Wang, Shengdian ; Ichikawa, Masao ; Rietz, Cecilia ; Flies, Dallas B. ; Lau, Julie S. ; Zhu, Gefeng ; Tamada, Koji ; Chen, Lieping. / Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. In: Cancer Research. 2005 ; Vol. 65, No. 3. pp. 1089-1096.
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