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Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors

Nature Medicine volume 3, pages 682–685 (1997)Cite this article

Abstract

The 4-1BB glycoprotein is a member of the tumor necrosis factor receptor superfamily1–4 and binds to a high-affinity ligand (4-1BBL) expressed on several antigen-presenting cells such as macrophages and activated B cells5,6. Expression of 4-1BB is restricted to primed CD4+ and CD8+ T cells7, and 4-1BB signaling either by binding to 4-1BBL or by antibody ligation delivers a dual mitogenic signal for T-cell activation and growth8–12. These observations suggest an important role for 4-1BB in the amplification of T cell-mediated immune responses. We now show that administration of anti-4-1BB monoclonal antibodies can eradicate established large tumors in mice, including the poorly immunogenic Ag104A sarcoma and the highly tumorigenic P815 masto cytoma. The immune response induced by anti-4-1BB monoclonal antibodies is mediated by both CD8+ and CD4+ T cells and is accompanied by a marked augmentation of tumor-selective cytolytic T-cell activity. Our data suggest that a similar approach may be efficacious for immunotherapy of human cancer.

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Author notes

  1. Robert S. Mittler and Lieping Chen: Correspondence should be addressed to L.C or R.S.M.

Authors and Affiliations

  1. Bristol-Myers Squibb Pharmaceutical Research Institute, 3005 First Avenue, Seattle, Washington, 98121, USA

    Ignacio Melero, Walter W. Shuford, Stephanie Ashe Newby, Alejandro Aruffo, Jeffrey A. Ledbetter, Karl Erik Hellström, Robert S. Mittler & Lieping Chen

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  1. Ignacio Melero
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Melero, I., Shuford, W., Newby, S. et al. Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat Med 3, 682–685 (1997). https://doi.org/10.1038/nm0697-682

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