Our laboratory's research is focused on the following two major areas:

1) Developing novel adoptive T cell therapy for the treatment of leukemia and lung cancer.

Human CD3+CD4-CD8-CD56- T cells, termed double negative (DN) T cells, compose a small population of peripheral T cells. Interestingly, DN T cells could also prevent death of recipients inoculated with a lethal dose of lymphoma. The function of human DN T cells was not known due to the low frequency of DN T cells and lack of specific markers to positively select them. Recently, we have developed a novel protocol by which therapeutic quality and quantity of human DN T cells can be obtained from peripheral blood of healthy donors by ex vivo expansion. More importantly, we have demonstrated that these ex vivo propagated human DN T cells have potent anti-tumour function both in vitro and in patient-derived xenograft models. DN T cells effectively target lung cancer and primary leukemic cells, including those that are resistant to chemotherapy while spare normal blood and bone marrow cells. Unlike conventional T cells, infusion of DN T cells does not cause tissue damage or graft-versus-host disease, supporting the safety of clinical use of DN T cells. Based on these findings, phase I clinical trials using DN T cells to treat patients with acute myeloid leukemia who are at high risk of disease recurrence has been started. As cryopreserved DN T cells from one healthy donor can target leukemic cells obtained from different patients in a non-HLA-restricted manner, it is possible to develop DN T cells as “off-the-shelf” living drugs. We are currently investigating the mechanisms by which these human DN T cells selectively recognize and kill cancer cells but not normal cells and tissues, and exploring the possibility of using DN T cells either alone or in combination with other therapies to eliminate cancer cells and prevent disease recurrence.

2) Dissecting cellular and molecular mechanisms involved in immunity and tolerance and their relevance in diseases.

The ability to induce unresponsiveness to our own tissue and transplanted cells, tissues and organ grafts while retaining immune responses towards viruses and malignant cells has been a dream of immunologists and clinicians for many years. To achieve this goal requires a deep understanding of the cellular and molecular mechanisms that control and regulate immune responses. Our lab has been studying the mechanisms by which immune regulatory T cells, particularly NK-CD3+ CD4 and CD8 double negative regulatory T cells (DN Tregs) in controlling immune related diseases. Our previous studies have demonstrated that treatment with murine DN Tregs resulted in suppressing allograft rejection, inhibiting autoimmune diseases and attenuating graft vs. host disease. We have now developed a novel protocol for large scale expansion of human DN Tregs. Another research focus of our laboratory is to understand the cellular and molecular mechanisms governing tolerance and immunity and to translate obtained knowledge into novel immunotherapies to treat graft-vs-host disease and transplant rejection using ex vivo expanded human DN Tregs.