Characterization and application of three novel monoclonal antibodies against human 4‐1BB: distinct epitopes of human 4‐1BB on lung tumor cells and immune cells

Abstract

4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is a costimulatory receptor that is primarily expressed on activated T cells and professional antigen-presenting cells. In this study, the expression pattern of 4-1BB on immunology cells and tumor cells was explored by flow cytometry using newly generated three anti-4-1BB monoclonal antibodies (mAbs; 6F9, 7D6, and 1G11), which bind to distinct 4-1BB epitopes. Compared with the available 4-1BB mAb 4B4-1 that recognized 4-1BB on activated T cells and monocytes, the novel mAbs also could recognize 4-1BB on some cancer cell lines, particularly on lung cancer cell lines such as SPC-A-1, H446, H460, and H1299 by flow cytometry analysis, western blot, and RT-PCR. Immunohistochemistry staining showed the 4-1BB was expressed on lung tumor tissue (33/35) but not on normal lung tissue (3/3). It was determined that 4-1BB was strictly expressed on lung cancer cells, which may provide information on the 4-1BB signal in tumor immunology mechanism.

Expression of 4-1Bb and Its Ligand on Blasts Correlates with Prognosis of Patients with Aml

“…4-1BB expression on cancer cells might play a relevant role by being expressed on solid tumor cells like osteosarcoma and lung cancer28 29 as well as on several subtypes of lymphoma. Expressed on granulocytes, its appearance on AML blasts is not surprising; however, the role in interaction with immunological effectors and intracellular blast-regulation is not yet clarified.…”

CD137 Is Required for M Cell Functional Maturation but Not Lineage Commitment

“…The induction of CD137 on intestinal epithelial cell lines was surprising, since it had previously been described mainly on bone marrow-derived cells such as activated T cells and myeloid cells, 39,40 though other reports on CD137 expression detected it specifically on vascular endothelial cells in the lung associated with tumors, 41 or associated with atherosclerosis. 42 The main known ligand for CD137 is the molecule 4-1BBL expressed on B cells and a variety of myeloid cells.…”

4-1BB (CD137), an inducible costimulatory receptor, as a specific target for cancer therapy

“…A number of studies have shown that 4-1BB is also expressed on a wide range of tumor cells, including SPC-A-1, H446, H460, and H1299 (19). Expression of 4-1BB in cancer patients was found also on tumor vessel walls, on the endothelial wall, on vascular smooth muscles (20), and in liver tissue (21).…”