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Blood, Vol. 93 No. 9 (May 1), 1999:
pp. 2999-3007
Inhibition of Human Breast Carcinoma Growth by a Soluble Recombinant
Human CD40 Ligand
Akio Hirano,
Dan L. Longo,
Dennis D. Taub,
Douglas K. Ferris,
Lawrence S. Young,
Arisitides G. Eliopoulos,
Angelo Agathanggelou,
Nicky Cullen,
James Macartney,
William C. Fanslow, and
William J. Murphy
From the Laboratory of Leukocyte Biology, National Cancer
Institute-Frederick Cancer Research and Development Center, Frederick;
Intramural Research Support Program, Science Applications
International Corporation (SAIC)-Frederick, Frederick, MD; National
Institute on Aging, Baltimore, MD; Cancer Research
Campaign (CRC) Institute for Cancer Studies, University of Birmingham
Medical School, Birmingham, UK; Histopathology Department, Walsgrave
Hospitals, Coventry, UK; and Immunex Inc, Seattle, WA.
CD40 is present on B cells, monocytes, dendritic cells, and
endothelial cells, as well as a variety of neoplastic cell types, including carcinomas. CD40 stimulation by an antibody has previously been demonstrated to induce activation-induced cell death in aggressive histology human B-cell lymphoma cell lines. Therefore, we wanted to
assess the effects of a recombinant soluble human CD40 ligand (srhCD40L) on human breast carcinoma cell lines. Human breast carcinoma
cell lines were examined for CD40 expression by flow cytometry. CD40
expression could be detected on several human breast cancer cell lines
and this could be augmented with interferon- . The cell lines were
then incubated with a srhCD40L to assess effects on in vitro growth.
srhCD40L significantly inhibited the proliferation of the
CD40+ human breast cancer cell lines. This inhibition
could also be augmented with interferon-. Viability was also
affected and this was shown to be due to increased apoptosis of the
cell lines in response to the ligand. Treatment of tumor-bearing mice
was then performed to assess the in vivo efficacy of the ligand.
Treatment of tumor-bearing SCID mice with the ligand resulted in
significant increases in survival. Thus, CD40 stimulation by its ligand
directly inhibits human breast carcinoma cells in vitro and in vivo.
These results suggest that srhCD40L may be of clinical use to inhibit human breast carcinoma growth.
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