The goal of Dr. Yang’s laboratory is to understand the molecular and cellular mechanisms leading to the generation of potent and long-lasting anti-tumor immunity, and to develop effective gene immunotherapeutic strategies for treating cancer. Furthermore, rational pre-clinical approaches will be tested in clinical trials in patients with Epstein-Barr virus (EBV)-related malignancies. Specifically, we focus on the following areas:
1. Innate Immunity to Viruses. Recombinant vaccinia virus and adenovirus have been developed as potent vaccine vehicles for treating cancer and infectious diseases. Recent studies have shown that the unique potency of these viruses lies in their effective activation of the innate immune system. How these viruses activate the innate immune system remains largely unknown. We have been interested in the role of pattern-recognition receptors including Toll-like receptors (TLRs)in innate immune recognition of these viruses as well as their signaling pathways. In addition, we are investigating the role of innate immune cells such as natural killer (NK) cells in innate and adaptive immune responses to these viruses. A full understanding of these processes will help us design effective vaccine strategies.
2. T Cell Memory. Eliciting long-lived memory T cell response is an ultimate goal of vaccination to provide long-term immunity against cancer. However, it is not clear what controls the formation of long-lived memory T cells. The understanding of mechanisms underlying memory T cell formation will provide important insights into the design of effective vaccines for treating cancer.
3. Regulatory T Cell Biology. Accumulating evidence has shown that the immunosuppressive CD4+CD25+Foxp3+ regulatory T cells (TReg) play a critical role in the suppression of anti-tumor immunity. However, little is known about how TReg suppress T cell activation in vivo. Delineation of mechanisms underlying TReg-mediated suppression in vivo will help develop strategies to overcome TReg-mediated suppression in favor of boosting anti-tumor immunity.
4. Immunotherapy for EBV-associated Malignancies. Clinically, EBV-associated malignancies such as Hodgkin’s lymphoma offer a unique model to explore antigen-defined immunotherapy approaches because EBV-derived tumor antigens are specific for tumor cells only. Using this clinical model, we will test the utility of rational strategies identified in our preclinical models.