Tim Luetkens
University of Maryland, Baltimore, MD·Microbiology & Immunology
One of the most powerful cancer treatments available takes a patient's own T cells, immune cells that kill infected or abnormal cells, and engineers them to carry a chimeric antigen receptor (CAR), a synthetic sensor that recognizes a protein on the surface of tumor cells. CAR T cells work well in blood cancers, but resistance is common and most patients who respond eventually relapse.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Biomedical Engineering
- Topics
CAR T cells
chimeric antigen receptor
trogocytosis
- Grants
- 1 known grant, through Aug 2027
What they work on
- Quantify the kinetics and molecular drivers of CAR-mediated trogocytosis, the stripping of target proteins from tumor cells onto CAR T cells, using high-resolution live-cell imaging and combinatorial T cell engineering.
- Determine how reducing a chimeric antigen receptor's binding affinity for its target antigen suppresses antigen transfer at the molecular and subcellular level without weakening tumor killing.
- Test how inhibiting cathepsin B, a protein-cutting enzyme made by T cells, affects antigen transfer and whether it improves long-term anti-tumor activity of CAR T cells.
- Benchmark affinity tuning, cathepsin B inhibition and cholesterol 25-hydroxylase overexpression for their effects on CAR T cell expansion, persistence and tumor control in culture and in vivo.
More about the research
One recently identified cause is CAR-mediated trogocytosis, in which the CAR physically pulls the target protein off the tumor cell and onto itself. The tumor cell loses the marker and becomes invisible to the therapy, while the CAR T cells now displaying the marker are killed by their own neighbors, shrinking the treating cell population and driving it into exhaustion. How this transfer happens at the molecular level is unknown, and no approved drug blocks it selectively.
Why it matters
Most patients treated with CAR T cells relapse, and antigen stripping from tumor cells is a major contributor to CAR T cell death and exhaustion. Identifying how this transfer works, and whether lowering receptor affinity, inhibiting cathepsin B or altering cholesterol metabolism can block it, could lead to engineered CAR T cell products that persist longer and control blood cancers more durably.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Sidi Chen
Yale University, CT·Biomedical Engineering
Advance and validate MAJESTIC, a gene delivery system combining mRNA, AAV vectors and the Sleeping Beauty transposon, testing efficient and stable cargo delivery with minimal toxicity across diverse immune cell types.
Peter Chockley
Ohio State University, OH·Microbiology & Immunology·Early-career
Develop monomeric chimeric antigen receptors (single-unit CARs with a stable off state) for natural killer cells, adding immune synapse augmentation, to reduce erratic signaling and improve killing of pediatric solid tumor cells.
Glenna Foight
Baylor College of Medicine, TX·Microbiology & Immunology
Determine how complexes of bZIP-family transcription factors, proteins that switch genes on or off, regulate T-cell exhaustion, using engineered protein inhibitors that block specific factors.
The school
University of Maryland, Baltimore: 23 labs on PI Pages, $1.5B a year on research, 79 research doctorates a year.
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