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Journal article
The efficacy of tumor debulking surgery is improved by adjuvant immunotherapy using imiquimod and anti-CD40
BMC Cancer, Vol.14
2014
Abstract
BACKGROUND
Tumor debulking surgery followed by adjuvant chemotherapy or radiotherapy is a standard treatment for many solid malignancies. Although this approach can be effective, it often has limited success against recurrent or metastatic cancers and new multimodality approaches are needed. Adjuvant immunotherapy is another potentially effective approach. We therefore tested the efficacy of the TLR7 agonist imiquimod (IMQ) combined with agonistic anti-CD40 in an incomplete debulking model of malignant mesothelioma.
METHODS
Established subcutaneous murine ABA-HA mesothelioma tumors in BALB/c mice were surgically debulked by 75% and treated with either: i) saline; ii) intratumoral IMQ; iii) systemic anti-CD40 antibody, or using a combination of IMQ and anti-CD40. Tumour growth and survival were monitored, and the role of anti-tumor CD4 and CD8 T cells in therapeutic responses was determined.
RESULTS
The combination therapy of partial debulking surgery, IMQ and anti-CD40 significantly delayed tumor growth in a CD8 T cell dependent manner, and promoted tumor regression in 25% of animals with establishment of immunological memory. This response was associated with an increase in ICOS+ CD8 T cells and tumor-specific CTL activity in tumor draining lymph nodes along with an increase in ICOS+ CD8 T cells in responding tumours.
CONCLUSIONS
We show that the post-surgical environment can be significantly altered by the co-administration of adjuvant IMQ and anti-CD40, resulting in strong, systemic anti-tumor activity. Both adjuvants are available for clinical use/trial, hence this treatment regimen has clear translational potential.
Details
- Title
- The efficacy of tumor debulking surgery is improved by adjuvant immunotherapy using imiquimod and anti-CD40
- Authors/Creators
- A. Khong (Author/Creator)A.L Cleaver (Author/Creator)M. Fahmi Alatas (Author/Creator)B.C. Wylie (Author/Creator)T. Connor (Author/Creator)S.A. Fisher (Author/Creator)S. Broomfield (Author/Creator)W.J. Lesterhuis (Author/Creator)A.J. Currie (Author/Creator)R.A. Lake (Author/Creator)B.W. Robinson (Author/Creator)
- Publication Details
- BMC Cancer, Vol.14
- Publisher
- BioMed Central
- Number of pages
- 9
- Identifiers
- 991005542045607891
- Copyright
- © 2014 Khong et al.
- Murdoch Affiliation
- School of Veterinary and Life Sciences
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.358 Dendritic Cell Therapy
- Web Of Science research areas
- Oncology
- ESI research areas
- Clinical Medicine