PhDSome recombinant bacterial strains have been shown to be very efficient in
experimental therapies against cancer in rodent models. Amongst them is an E. coli
that expresses the Listeriolysin-O protein (LLO) and a model tumour antigen
ovalbumin (OVA). I have demonstrated the efficacy of E. coli-LLO/OVA in preventive
or therapeutic models against OVA-expressing tumours. This effect is mediated by
specific cytotoxic T-lymphocytes (CTL) against OVA antigen and inhibition of the
suppressive function of Foxp3+ T-regulatory (Treg) cells. When applying a “real” and
clinically-relevant tumour antigen, Wilms’ tumour-1 antigen (WT1), this vaccine (E.
coli-LLO/WT1) is capable of inducing an anti-tumour effect. Furthermore, we have
characterised the immunodominant epitope involved in E. coli-LLO/WT1-
immunisation (pWT130-138, NAPYLPSCL) through screening of a peptide library of the
WT1 protein by cytokine ELISpot, lymphocyte stimulation effects, MHC stability, and
specific cytotoxicity. Also, the effect on Treg when applying a real tumour antigen is
still preserved. Co-injection of pWT130-138 with E. coli-LLO resulted in an anti-tumour
effect equivalent to that obtained with E. coli-LLO/WT1, demonstrating that the
adjuvant properties of the E. coli-LLO vaccine can be exploited in conjunction with
peptides.
Treg are recognised as playing important roles in immunotherapy. An ideal
vaccine for cancer would stimulate specific cytotoxic responses and suppress Treg
function. This study showed that E. coli-LLO vaccine suppresses Treg cell function
and the Treg RNA microarray analysis revealed expression differences of some
cytokine/chemokine genes which could be relevant to the reversal of Treg
suppression. This may have important implications for developing anti-tumour
vaccine strategies in humans. Overall, this study demonstrated that an E. coli-LLO
vaccine is effective in cancer immunotherapy, either co-expressed with a real tumour
antigen or co-injected with a peptide. The efficacy of this vaccine was due to its
ability to dampen Treg suppressive function