Recombinant CD40 ligand therapy has significant antitumor effects on CD40-positive ovarian tumor xenografts grown in SCID mice and demonstrates an augmented effect with cisplatin

Sharad A Ghamande, Shashikant Lele, Bonnie L. Hylander, Ezogelin Oflazoglu, Elizabeth A. Repasky, William Fanslow

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

CD40 is a member of the tumor necrosis factor receptor family and was first identified with a monoclonal antibody raised against bladder carcinoma. Recombinant human CD40L has been shown previously to have a direct antitumor effect on an ovarian cancer cell line and ovarian carcinoma cells isolated from ascites fluid. We show here that rhuCD40L inhibits the growth of several ovarian adenocarcinomas derived from surgical specimens and grown as xenografts in severe combined immunodeficient mice. Two 14-day treatment cycles were more effective than one. This effect is apparently not mediated by natural killer cells, because blocking natural killer cell activity by antiasialo GM-1 did not diminish this effect. In addition to suppression of tumor growth, treatment with rhuCD40L resulted in an increased expression of FasL, an increase in apoptosis, and histological changes including increased fibrosis and areas of tumor destruction. Using this model, we examined the efficacy of rhuCD40L in combination with chemotherapeutic agents. The antitumor effect of rhuCD40L in combination with 4 mg/kg cisplatin (CDDP) was increased over the effect of CDDP alone. Furthermore, rhuCD40L increased the efficacy of a suboptimal dose of CDDP (2mg/kg) such that it matched that of high-dose CDDP alone. These data suggest a role for rhuCD40L therapy in combination with platinum based regimens for primary treatment of epithelial ovarian tumors.

Original languageEnglish (US)
Pages (from-to)7556-7562
Number of pages7
JournalCancer Research
Volume61
Issue number20
StatePublished - Oct 15 2001
Externally publishedYes

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CD40 Ligand
SCID Mice
Heterografts
Cisplatin
Natural Killer Cells
Carcinoma
Neoplasms
Tumor Necrosis Factor Receptors
Growth
Platinum
Ascites
Ovarian Neoplasms
Urinary Bladder
Adenocarcinoma
Fibrosis
Therapeutics
Monoclonal Antibodies
Apoptosis
Cell Line

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Recombinant CD40 ligand therapy has significant antitumor effects on CD40-positive ovarian tumor xenografts grown in SCID mice and demonstrates an augmented effect with cisplatin. / Ghamande, Sharad A; Lele, Shashikant; Hylander, Bonnie L.; Oflazoglu, Ezogelin; Repasky, Elizabeth A.; Fanslow, William.

In: Cancer Research, Vol. 61, No. 20, 15.10.2001, p. 7556-7562.

Research output: Contribution to journalArticle

Ghamande, Sharad A ; Lele, Shashikant ; Hylander, Bonnie L. ; Oflazoglu, Ezogelin ; Repasky, Elizabeth A. ; Fanslow, William. / Recombinant CD40 ligand therapy has significant antitumor effects on CD40-positive ovarian tumor xenografts grown in SCID mice and demonstrates an augmented effect with cisplatin. In: Cancer Research. 2001 ; Vol. 61, No. 20. pp. 7556-7562.
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