Our Work
B cell engineering
We engineer B cells for the expression of desired antibodies against infectious diseases and cancer. The transgenic antibody is expressed first as a membrane bound B cell receptor (BCR) allowing antigen-induced activation of the B cell. In a first application, as a potential single-shot HIV therapy, we engineered B cells using CRISPR/Cas9 to express anti-HIV broadly neutralizing antibodies (bNAbs). We demonstrated that, upon immunization of mice, adoptively transferred engineered B cells home to germinal centers (GC) where they predominate over the endogenous response and differentiate into memory and plasma cells while undergoing class switch recombination (CSR). Immunization with a high affinity antigen increases accumulation in GCs and CSR rates. Boost immunization increases the rate of engineered B cells in GCs and antibody secretion, indicating memory retention. Finally, antibody sequences of engineered B cells in the spleen show patterns of clonal selection. Therefore, we uniquely engineered B cells as a living and evolving drug.
T cell engineering
In recent years, T cells engineered to express chimeric antigen receptors (CARs) directed against CD19 have led to unprecedented rates of complete responses in B-cell acute lymphoblastic leukemia, chronic lymphoblastic leukemia, and diffuse large B-cell lymphoma. These remarkable results prompted the Food and Drug Administration approval of several anti-CD19 CAR T cell therapies. However, many challenges remain. Treatment is often associated with cytokine release syndrome and sometimes further leads to neurotoxicity. In addition, many patients may still relapse with a CD19-negative blast or a CD19-positive blast following CAR-T exhaustion and depletion. Furthermore, T-cell responses represent only one of many potentially therapeutic responses, and the genetic manipulation of other immune cells is at a much earlier stage of development. Most importantly, the great potential of immune gene therapy is yet to be manifested in the treatment of solid tumors and autoimmune diseases or in organ transplantations. In our lab, we use novel technologies to engineer T cells ex vivo as well as in vivo for the expression of diverse CARs and TCRs tackling liquid and solid tumors, allergy promoting IgE B cells and more