Inhibition of human breast carcinoma growth by a soluble recombinant humanCD40 ligand

CD40 is present on B cells, monocytes, dendritic cells, and endothelial cel ls, as well as a variety of neoplastic cell types, including carcinomas. CD 40 stimulation by an antibody has previously been demonstrated to induce ac tivation-induced cell death in aggressive histology human B-cell lymphoma c ell lines. Therefore, we wanted to assess the effects of a recombinant solu ble human CD40 ligand (srhCD40L) on human breast carcinoma cell lines. Huma n breast carcinoma cell lines were examined for CD40 expression by flow cyt ometry, CD40 expression could be detected on several human breast cancer ce ll lines and this could be augmented with interferon-gamma. The cell lines were then incubated with a srhCD40L to assess effects on in vitro growth. s rhCD40L significantly inhibited the proliferation of the CD40(+) human brea st cancer cell lines. This inhibition could also be augmented with interfer on-gamma. Viability was also affected and this was shown to be due to incre ased apoptosis of the cell lines in response to the ligand. Treatment of tu mor-bearing mice was then performed to assess the in vivo efficacy of the l igand. Treatment of tumor-bearing SCID mice with the ligand resulted in sig nificant increases in survival. Thus, CD40 stimulation by its ligand direct ly inhibits human breast carcinoma cells in vitro and in vivo. These result s suggest that srhCD40L may be of clinical use to inhibit human breast carc inoma growth.