Enhancement of humoral and cellular immunity with an anti-glucocorticoid-induced tumour necrosis factor receptor monoclonal antibody

SummaryAdjuvants, including antibodies to tumour necrosis factor receptor super-family members, augment immune responses. One member of this family,glucocorticoid-induced tumour necrosis factor receptor (GITR), isexpressed at low levels on naive/resting T cells, B cells and macrophages,but at higher levels on T regulatory cells. The aim of this study was todetermine the ability of a rat anti-mouse GITR monoclonal antibody,2F8, to stimulate murine humoral and cellular immunity in a prime boostmodel with particular attention to posology and antigen-specific effects.2F8 enhanced the humoral immune response to ovalbumin and haemag-glutinin (HA) compared with controls and this enhancement was equal toor greater than that obtained in mice dosed with standard adjuvants. 2F8F(ab 0 ) 2 fragments were as effective as intact antibody in boosting humoralimmunity, indicating that FcR-mediated cross-linking of 2F8 is notrequired for efficacy. Moreover, the enhanced response was durable andantigen specific. Administration of 2F8 shifted the immune responsetowards a T helper type 1 response with significant enhancement ofimmunoglobulin G2a- and G2b-specific anti-HA antibodies, as well asenhanced cellular immunity as measured by ELISPOT. 2F8-treated micealso generated significantly more neutralizing antibodies to HA than con-trol mice. Our findings show that anti-GITR is a robust, versatile adjuvantthat, unlike commonly used adjuvants that primarily enhance humoralimmunity, enhances both humoral and cellular immunity. These resultssupport the continued development of anti-GITR for such indications ashaematological and solid tumours, chronic viral infections, and as a vac-cine adjuvant.Keywords: adjuvant; glucocorticoid-induced tumour necrosis factor recep-tor; haemagglutinin; T helper type 1 response; tumour necrosis familyreceptor superfamily