Transplant and Cellular Therapy

Transplant and Cellular Therapy Program Summary The central scientific theme of the TCT Program is that immune cells and hematopoietic stem cells can be engineered to overcome the principal obstacles that limit the success of allogeneic hematopoietic stem cell transplantation (alloHSCT)—graft-versus-host disease (GVHD), prolonged immune incompetence, conditioning toxicities, and relapse—and of immune effector cell therapies—on-target/off-tumor tissue injury, cytokine release syndrome, and immune cell-associated neurotoxicity syndrome—as well as logistical barriers and cost. Cell therapies are also more exportable than alloHSCT, helping to meet the Cancer Center’s goal of broadening access to novel cancer therapies in Greater Minnesota (outside of the Twin Cities). The Program has 4 Aims to address this overarching theme: 1) Identify safer alternatives to αβT-cell immune effector cells as “off-the-shelf” allogeneic immunotherapies, including the development of chimeric antigen receptors with greater specificity in order to maximize tumor kill and reduce on-target/off-tumor side effects; 2) Introduce novel engineering approaches to extend persistence and control proliferation of engineered IECs in vivo and establish large-scale manufacturing methods for producing hundreds of doses of a well-defined, quality-controlled, off-the-shelf product; 3) Explore nonchemotherapy approaches for lymphodepletion that are nontoxic (eg, no myelosuppression) and safer; and 4) Develop novel pharmacologic and cellular interventions to prevent acute and chronic GVHD and eliminate the prolonged immune incompetence commonly observed after alloHSCT. TCT is co-led by John E. Wagner, MD, an experienced clinical and translational investigator in the field of HSCT and cellular therapeutics, and Brian C. Betts, MD, a physician-scientist with expertise in signal transduction, immune tolerance, and cell therapy. TCT has 34 members, representing 9 departments and 5 schools or colleges. For the last budget year, these members were supported by cancer-relevant research funding of $11.6 million in direct costs, of which $0.8 million came from the NCI. Since 2018, Program members have published 850 papers, 36% of which resulted from intraprogrammatic collaborations, 22% from interprogrammatic collaborations, and 76% from external collaborations. The Masonic Cancer Center supports the Program by providing Shared Resources with state-of-the-art technologies such as mass spectrometry and flow cytometry, as well as the Clinical Trials Office, which is critical to the implementation and oversight of numerous complex early-phase clinical trials.