Anti 4-1BB monoclonal antibodies activate T-cells and eradicate established tumors (Meeting abstract).

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

Anti 4-1BB monoclonal antibodies activate T-cells and eradicate established tumors (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 38:A2320 1997. Unique Identifier : AIDSLINE ICDB/98639320
Melero I; Shuford WS; Ashe Newby S; Aruffo A; Ledbetter JA; Hellstrom KE; Mittler RS; and Chen L; Bristol-Myers Squibb Pharmaceutical Research Institute, 3005; First Avenue, Seattle, WA 98121

Abstract: The 4-1BB glycoprotein is a member of the tumor necrosis factor receptor superfamily and binds to a high affinity ligand expressed on several antigen-presenting cells such as macrophages and activated B-cells. Expression of 4-1BB is restricted to primed CD4+ and CD8+ T-cells and signaling either by binding to its natural ligand or by antibody ligation delivers a co- mitogenic signal for T-cell activation and growth, suggesting an important role for 4-1BB in the amplification of a T-cell mediated immune response. We now show that administration of anti 4-1BB monoclonal antibodies (mAbs) can eradicate established large tumors in mice, including the poorly-immunogenic Ag104A sarcoma and the highly-tumorigenic P815 mastocytoma. The anti 4-1BB mAbs-induced tumor immunity is mediated by both CD8+ and CD4+ T-cells with a marked augmentation of tumor-specific cytolytic T-cell activity. The potent antitumor activity of anti 4-1BB mAbs even against large, poorly-immunogenic mouse tumor indicates that a similar approach holds promise for immunotherapy of human cancer.

Keywords: Animal Antibodies, Monoclonal/PHARMACOLOGY/*THERAPEUTIC USE CD4-Positive T-Lymphocytes/*IMMUNOLOGY CD8-Positive T-Lymphocytes/*IMMUNOLOGY Immunity, Cellular *Immunotherapy Mice Sarcoma, Experimental/*IMMUNOLOGY/*THERAPY ABSTRACT
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M9820756

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