John Wagner
University of Minnesota, MN·Medicine & Clinical Research
Engineered immune cells can now cure some blood cancers once thought incurable. In chimeric antigen receptor (CAR) T-cell therapy, a patient's own T cells are given a synthetic receptor that recognizes a cancer marker.
- Fields
Medicine & Clinical Research
Microbiology & Immunology
Biomedical Engineering
- Topics
CAR-T cell therapy
chimeric antigen receptor
regulatory T cells
- Grants
- 3 known grants, through Jan 2029
What they work on
- Establish the safety and maximum tolerated dose of donor CAR19 regulatory T cells, given with and without IL-2, in patients with relapsed or refractory CD19+ acute lymphocytic leukemia, measuring cell persistence and tumor killing.
- Engineer CAR19 Tregs to carry an orthogonal IL-2 receptor that responds only to a matched designer IL-2. This aims to boost persistence and tumor killing without the side effects of body-wide IL-2.
- Test nanoCAR Tregs that target CD83 on acute myeloid leukemia cells while sparing normal blood-forming progenitors, and add a drug-inducible CAR switch to limit exhaustion and improve safety.
- Test whether off-the-shelf CD83 CAR CD8 Tregs derived from induced pluripotent stem cells can be engineered to avoid rejection and exhaustion while keeping strong killing activity against AML.
- Test whether combining engineered iPSC-derived NK cells with tri-specific killer engagers (TriKEs) and CARs improves the specificity, potency and persistence of AML killing.
- Develop drug and cell treatments to prevent acute and chronic graft-versus-host disease and restore immune function after donor stem cell transplants, alongside safer, chemotherapy-free ways to prepare patients for cell infusion.
More about the research
Making a custom product for each patient is slow and costly, however, and quality varies. The cells can also tire out (exhaustion), miss cancer cells that stop showing the marker, damage healthy tissue that carries the same marker, and trigger cytokine release syndrome (CRS), a dangerous wave of inflammation. The lab's work aims to build safer "off-the-shelf" cell therapies made from donor cells, which could be produced in large batches and given to many patients. It also works on improving stem cell transplants.
Why it matters
Patients with blood cancers such as acute lymphocytic leukemia and acute myeloid leukemia could benefit from ready-made donor cell therapies. Such therapies may cost less, reach patients faster and be available more widely than personalized CAR-T products. They could also carry lower risks of cytokine release syndrome and harm to healthy tissue. The transplant work could help reduce graft-versus-host disease and lasting immune weakness after stem cell transplants, and help bring these therapies to patients in Greater Minnesota.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jeffrey Miller
University of Minnesota, MN·Microbiology & Immunology
Engineer iPSC-derived NK (iNK) cells with gene edits that improve homing and migration into tumors, tolerance of low oxygen (hypoxia), and survival after transfer into patients with solid tumors.
Jaebok Choi
Washington University in St Louis, MO·Microbiology & Immunology
Test whether drug blockade of VLDLR, a receptor on T cells, prevents graft-versus-host disease while preserving the graft-versus-leukemia effect, in two independent mouse models of allogeneic hematopoietic cell transplantation.
Antonia Rotolo
University of Pennsylvania, PA·Microbiology & Immunology
Generate optimized CAR-iNKT cells for solid tumors by pairing high-performing variants of the natural iNKT cell receptor (iTCR) with chimeric antigen receptor constructs that redirect the cells to tumor markers.
The school
University of Minnesota: 88 labs on PI Pages, $1.4B a year on research, 722 research doctorates a year.
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