Weiguo Cui Laboratory

Current Research Interests

T Cell Memory

During an acute viral or bacterial infection, naïve T cells can differentiate into multiple types of effector and memory T cells that help to mediate pathogen clearance and provide long-term protective immunity. The main goal of our research in the lab is to elucidate how TCR and cytokine signaling and their downstream transcriptional programs regulate pathogen-specific T cells to proliferate, or differentiate into either short-lived effector cells or long-lived memory cells.

T Cell Differentiation in Chronic Function

During persistent inflammation in chronic viral infections, CD8 T cells are thought to become “exhausted,” a term signifying loss of their normal cytotoxic function. However, recent work from our lab and others has shown that some CD8 T cells in chronic viral infection do not become “exhausted” and instead retain their cytotoxic function.

We are currently investigating what factors allow CD8 T cells to maintain their cytotoxic capacity, how CD4 T cells are involved in generating or regulating these factors, and how to leverage these factors to improve control over chronic viral infections.

Figure 1: CD4+ T Cell Help Is Required for the Formation of a Cytolytic CD8+ T Cell Subset that Protects against Chronic Infection and Cancer. Zander, et al. Immunity. 2019

Adoptive Cell Transfer for Cancer

Tumors are known to establish an immunosuppressive tumor microenvironment (TME) that prevents CD8 T cells from killing tumor cells. Administration of attenuated bacteria directly into tumor sites is known to promote inflammation and improve tumor control.

Our lab has developed a method termed ReACT (Reenergized Adoptive Cell Transfer) in which tumor-reactive CD8 T cells are transduced with a chimeric antigen receptor (CAR) specific for a bacterial antigen.

Figure 2: ReACT therapy combines BCG-CAR transduced T cells and intravesical instillation of BCG to treat bladder cancer. (Patent: US 2018/0334651)

Co-administration of these modified T cells and bacteria into the tumor site significantly improves tumor control compared to standard CAR T cells or bacterial injection alone. We are currently working on advancing and improving this technology to advance treatment for solid tumors.

Adoptive Cell Transfer for Cancer

Tumors are known to establish an immunosuppressive tumor microenvironment (TME) that prevents CD8 T cells from killing tumor cells. Administration of attenuated bacteria directly into tumor sites is known to promote inflammation and improve tumor control. Our lab has developed a method termed ReACT (Reenergized Adoptive Cell Transfer) in which tumor-reactive CD8 T cells are transduced with a chimeric antigen receptor (CAR) specific for a bacterial antigen. Co-administration of these modified T cells and bacteria into the tumor site significantly improves tumor control compared to standard CAR T cells or bacterial injection alone. We are currently working on advancing and improving this technology to advance treatment for solid tumors.