Antonia Rotolo
University of Pennsylvania, PA·Microbiology & Immunology
Cancers that form solid masses in organs and tissues are much harder to treat with engineered immune cell therapies than blood cancers are, partly because the area immediately around a tumor suppresses immune attack. Work here centers on a rare immune cell type, the invariant natural killer T (iNKT) cell, an innate-like T cell that recognizes targets through CD1d, a molecule present in the same form in everyone rather than varying between people.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Biomedical Engineering
- Topics
iNKT cells
invariant natural killer T cells
CAR T cell therapy
- Grants
- 1 known grant, through Jun 2031
What they work on
- 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.
- Define how iTCR optimization improves CAR-iNKT killing, proliferation and immune-modulating activity, and assess safety and effects on the suppressive tumor microenvironment in humanized mice carrying human immune cells and tumors.
- Test optimized CAR-iNKT cells in pet dogs with spontaneous solid cancers, a large-animal system whose tumor and immune biology resembles human disease, to gather translational efficacy and safety data.
- Determine which iTCR differences explain the donor-to-donor variability seen in CAR-iNKT products, comparing human and canine iNKT cells to identify receptor features linked to stronger function.
More about the research
Because iNKT cells react to a shared molecule, they can be made from healthy donors and given to unrelated patients without causing graft-versus-host disease, the attack on host tissue that normally limits donor cell therapies. That makes them attractive for "off-the-shelf" products, and they can also be fitted with chimeric antigen receptors (CARs), engineered proteins that direct a cell to a chosen tumor marker.
Why it matters
Many patients with solid tumors do not respond to existing immunotherapies. By making donor-derived iNKT cell products more consistently potent, this work could help build ready-to-use cell therapies that function inside the hostile environment of a tumor. Pet dogs with spontaneous cancers and no remaining treatment options would be treated directly, and the resulting data may speed testing in children and adults with currently incurable cancers.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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.
John Wagner
University of Minnesota, MN·Medicine & Clinical Research
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.
Seth Pollack
Northwestern University, IL·Medicine & Clinical Research
Determine a safe and effective dose of B10G5, an antibody that neutralizes the tumor-shed immune-suppressing protein MIC, and test whether it activates NK cells within canine soft tissue sarcomas.
The school
University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.
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