Targeted immunotherapies for hematologic malignancies

Our overall goal is to develop novel targeted immunotherapies for patients with hematologic malignancies. The group develops adoptive T cell therapies with native or engineered receptors and evaluates combinatorial strategies. The objective is to efficiently target tumor cells, mitigate immunosuppressive tumor microenvironment factors, favor tumor-targeted migration and longevity of transferred T cells, control potential toxicities, identify novel personalized targets, and move developments to the clinic.

• To engineer human T cells for targeting hematologic malignancies (chimeric antigen receptors, transgenic T cell receptors, engager molecules etc)

• To determine if function and persistence of transgenic T cells can be enhanced through (a) reactivating viruses, (b) immune checkpoint blockade or (c) vaccination

• To develop combinatorial approaches to T cell therapy targeting both the tumor cells and their microenvironment (e.g. engineer tumor-directed migration, resistance to immune inhibitory signals)

• To engineer signaling switches in T cells that revert tumor-associated immune inhibitory signals.

• To evaluate 3D culture systems to better model the tumor microenvironment in vitro and apply them to evaluate transgenic T cell function

• To identify immunogenic mutational tumor neo-antigens in patients with hematologic malignancies and to isolate their neo-antigen specific TCRs for personalized medicine applications.

• We apply principles from immunology, hematology, cancer and systems biology, use gene transfer and editing technologies to engineer T cells, and collaborate with experts in protein engineering, gene editing, proteomics/ peptidomics, immunomonitoring, bioinformatics, bioengineering, clinical hematology and immuno-oncology.