Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

Agonistic Anti-CD40 Antibody Therapy is Effective Against Postoperative Cancer Recurrence and Metastasis in a Murine Tumor Model

Khong, Andrea*,†; Brown, Matthew D.*,‡; Vivian, Justin B.; Robinson, Bruce W. S.*,†; Currie, Andrew J.§

doi: 10.1097/CJI.0b013e31829fb856
Basic Studies

Postresection recurrences of cancer arising from occult tumor deposits, either local or metastatic, represent major causes of death in patients with operable solid tumors. Thus, new therapies are required that complement existing treatments to eradicate these occult deposits. Agonistic anti-CD40 antibody is one of the most powerful new cancer immunotherapies, enhancing immune priming of effector CD8 T cells by dendritic cells, leading to increased antitumor activity. We investigated the use of anti-CD40 antibody for the treatment of postoperative recurrence and metastasis, with regional lymphadenectomy, in a murine model of cancer. Subcutaneous AB1-HA mesothelioma tumors were induced in BALB/c mice. Established tumors were surgically excised on day 16, with or without sentinel lymph node removal. On the day of surgery, animals were rechallenged with AB1-HA tumor cells at the surgical site (local recurrence) or the opposite flank (metastasis). Postoperative tumors were treated with anti-CD40 (FGK45) on emergence, delivered either intratumorally, peritumorally, or systemically. Local or systemic anti-CD40 treatment slowed postsurgical metastatic growth relative to untreated controls (P=0.020) and improved survival from metastasis. Anti-CD40 also retarded the growth of local recurrences (P=0.004) and improved survival from recurrence. Sentinel lymph node dissection did not impair efficacy (P>0.05). This study demonstrates that anti-CD40 therapy, given either locally or systemically, may be a powerful and readily translatable adjuvant to cancer surgery, including in cases where regional lymphadenectomy is indicated.

*Tumour Immunology Group, School of Medicine and Pharmacology, University of Western Australia

National Centre for Asbestos Related Diseases

Department of Surgery, Urological Research Centre/University, Sir Charles Gairdner Hospital

§School of Veterinary and Biomedical Sciences, Murdoch University, Perth, WA, Australia

A.K. and M.D.B. contributed equally.

Reprints: Andrew J. Currie, School of Veterinary & Life Sciences, Murdoch University, South Street, Murdoch, Western Australia 6150, Australia (e-mail:

Received December 12, 2012

Accepted April 28, 2013

© 2013 by Lippincott Williams & Wilkins