The role of CD40 and CD137 in immune responses to cancer : a study of monoclonal antibody mediated immunomodulation in two murine tumour models

Abstract

Specific monoclonal antibodies (mAb) against CD40 and CD137 were used to deliver a signal through the ligation and crosslinking of the surface receptor. The character of these responses and potential for immunotherapy were investigated in vitro and in vivo using two murine cancer models, CT26 and B16.

FACS analysis of CT26 and B16 demonstrated that neither expresses CD40 or CD137. Furthermore the mAb used, FGK45, 3/23 (CD40) and Lob 12 (CD137), had no effect on tumour growth in vitro.

CT26-bearing BALB/c and B16-bearing C57B16 mice were treated with anti-CD40 mAb. Growth of established subcutaneous (sc) and intradermal (id) CT26 was significantly reduced. In contrast there was no protection from pulmonary CT26. Pulmonary B16 deposits were significantly reduced with anti-CD40 mAb.

The pulmonary CD8⁺ lymphocyte population increased in response to anti-CD40 mAb. In BALB/c mice this was partly tumour dependent, but tumour independent in C57B16 mice. The CD19⁺ population also expanded but the CD4⁺ cell number was unaffected by anti-CD40 mAb.

The response to anti-CD40 mAb was found to involve IFN-γ, but this cytokine alone had no in vivo effect on the growth of CT26, suggesting that anti-CD40 mAb was not effective merely through increased levels of IFN-γ.

Selective depletion of CD4⁺ and CD8⁺ cells demonstrated that tumour abrogation with anti-CD40 mAb was dependent on CD8⁺ cells, but did not require CD4⁺ cells. The specific effector cells could not be isolated in vitro.

Transfection of CD40 ligand into CT26 cells gave greatly enhanced protection against tumour growth compared with anti-CD40 mAb.

Immunomudulation through CD40 and CD137 can result in a powerful and enduring response to tumour antigen that may be useful in the development of novel strategies in cancer immunotherapy.

More information

Identifiers

Catalogue record

Export record

ASCII CitationAtomBibTeXData Cite XMLDublin CoreDublin CoreEP3 XMLEndNoteHTML CitationHTML CitationHTML ListJSONMETSMODSMPEG-21 DIDLOpenURL ContextObjectOpenURL ContextObject in SpanRDF+N-TriplesRDF+N3RDF+XMLRIOXX2 XMLReferReference ManagerSimple Metadata