Enhancing the efficacy of Adoptive cellular Immunotherapy for cancer

Researchers in the Darcy Laboratory aim to develop effective immunotherapies for cancer. Projects seek to turn the disease-fighting capacity of the immune system against cancer cells by genetically modifying immune system cells to respond against cancer. Various types of cells are used including natural killer cells, dendritic cells and several types of T cells. Combination therapies are also investigated, where gene-modified immune cells are combined with drugs or vaccines to produce the optimal anti-tumour treatment. Most studies are preclinical in nature with a view towards clinical translation, in which final preparations of genes and cells are made ready for use in clinical trials.

It is becoming increasingly apparent that engaging anti-tumour immune responses is fundamental for effective cancer treatment. However, in many cancer types, the immune system remains ‘ignorant’ of the cancer leading to the absence of tumour-infiltrating lymphocytes. One effective therapeutic option is a process called adoptive immunotherapy. This involves genetically engineering a patient’s peripheral blood lymphocytes with a chimeric antigen receptor (CAR) enabling recognition of tumour antigen, expanding these cells ex vivo and then reinfusion back into the patient.

These CAR T cells have been shown to be highly effective in haematological malignanices but have had little impact on other cancer types. Generally speaking these expanded CAR T cells predominantly consist of conventional CD8+ and CD4+ T cells. However, the importance and contribution of other cell types within this population such as NK cells, NKT cells and MAIT cells is not understood.

Using a highly novel transgenic mouse in which all immune cells express the Chimeric Antigen Receptor, this project would evaluate the potential of these immune subsets to promote an anti-tumour immune response both in vitro and in vivo. Techniques that will be used include, cell culture, flow cytometry, chromium release assay, ELISA, cytometric bead array and in vivo mouse experiments.

This project will therefore seek to identify novel combination therapies that may have clinical relevance and consequently investigate the mechanism by which the anti-tumor immune response is enhanced. The project will involve a number of molecular and biochemical methods including flow cytometry, ELISA and ex vivo stimulation of isolated immune subsets. The student will become competent in tissue culture and the handling of mice. We are looking for a highly motivated student with an interest in immunology and the development of cancer therapeutics.

Researchers in the Darcy Laboratory aim to develop effective immunotherapies for cancer. Projects seek to turn the disease-fighting capacity of the immune system against cancer cells by genetically modifying immune system cells to respond against cancer. Various types of cells are used including natural killer cells, dendritic cells and several types of T cells. Combination therapies are also investigated, where gene-modified immune cells are combined with drugs or vaccines to produce the optimal anti-tumour treatment. Most studies are preclinical in nature with a view towards clinical translation, in which final preparations of genes and cells are made ready for use in clinical trials.
The lab closely collaborates with other groups in the Cancer Immunology Research Program, including the Kershaw/Immune Innovation Lab and the Neeson/Haematology Immunology Translational Research Lab (HITRL).