Does blockade of myeloid derived suppressor cells enhance the control of metastatic disease when combined with chemotherapy or MEK targeted therapy?

For breast cancer patients whose disease recurs and develops as secondary tumours (metastases) after apparently successful primary tumour therapy, the long term outlook is not good. This is more likely to occur in patients with triple negative breast cancer (TNBC), that is, cancers that lack expression of ER, PR and Her2 and are therefore not suitable for treatment with endocrine therapy or with antibodies against Her2. Oncologists have an increasing number of agents available to treat patients with TNBC, but in nearly all cases, disease stabilization is the goal, rather than cure. We aim to develop new therapies that provide a long-term remission and possible cure for these patients. The idea for this therapy that we are proposing came from results in a study that we recently published. We demonstrated that removal of a type of immune cell that represses anti-tumour activity of other immune cells caused a profound inhibition of the development of metastatic disease in preclinical trials of metastatic cancer in mice. We remove these immune suppressing cells using an antibody against a protein called granulocyte-colony stimulating factor receptor, or G-CSFR, for short. Here we will test this new antibody in combination with standard chemotherapy or in combination with another new drug that targets a particular tumour-promoting gene, using our preclinical models of advanced breast cancer in mice.

If successful, these new combination therapies could be fast-tracked into Phase1/11 clinical trials.