Yvonne Yu-Hsuan Chen
University of California-Los Angeles, CA·Biomedical Engineering
Glioblastoma is the most common primary brain tumor, and only about 5.5% of patients survive five years. One promising treatment is CAR-T cell therapy.
- Fields
Biomedical Engineering
Microbiology & Immunology
Medicine & Clinical Research
- Topics
glioblastoma
brain tumor
CAR-T cell therapy
- Grants
- 2 known grants, through Jan 2028
What they work on
- Test whether bispecific IL-13Rα2/TGF-β CAR-T cells, which target a tumor marker and turn the suppressive signal TGF-β into a stimulant, clear glioblastoma and trigger immunity against tumor cells lacking the marker, in mouse models of mixed tumors.
- Profile how these CAR-T cells change the immune makeup of the tumor using flow cytometry, CyTOF, single-cell RNA sequencing and T-cell receptor sequencing to measure epitope spreading.
- Evaluate the safety of IL-13Rα2/TGF-β CAR-T cells with worst-case stress tests in immunocompetent mice, then verify efficacy in fresh patient biopsies and patient-derived tumor (GliomaPDOX) mouse models.
- Optimize clinical-grade manufacturing of IL-13Rα2 CAR-T cells armored with the immune-boosting signals IL-12 and DR-18.
- Run a first-in-human trial of IL-13Rα2/IL-12/DR-18 CAR-T cells for recurrent glioblastoma, and identify biomarkers of response and mechanisms of resistance.
More about the research
In this approach, a patient's T cells, the immune system's killer cells, are engineered with a chimeric antigen receptor (CAR), a synthetic receptor that helps them find a specific marker on tumor cells. In glioblastoma, the results have been safe but weak, for two main reasons. Tumor cells vary in which markers they carry, so cells that lack the target escape. The tumor microenvironment (TME), the tissue and cells surrounding the tumor, also suppresses immune attack. This work engineers CAR-T cells that both kill tumor cells directly and reshape the TME so the body's own immune system joins in.
Why it matters
Patients with glioblastoma have few effective options. CAR-T cells that both attack tumor cells and overcome the tumor's immune suppression may lead to better immunotherapy for this cancer. The work will produce preclinical safety and efficacy data to support a phase 1 trial. It will also provide first-in-human data on feasibility, safety and response biomarkers for patients with recurrent glioblastoma.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
David Akhavan
University of Kansas, KS·Biomedical Engineering
Develop nanocarriers, tiny drug-carrying particles, that can be loaded into CAR T cells, which are engineered tumor-targeting immune cells, to create a platform for delivering drugs into glioblastoma.
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.
Mohamad Hamieh
Weill Medical College of Cornell University, NY·Microbiology & Immunology
Test strategies to reduce ICANS, the neurotoxicity of CAR T-cell therapy, by targeting extracellular vesicles released by activated CAR T cells, using animal models that track blood-brain barrier integrity and antitumor activity.
The school
University of California-Los Angeles: 84 labs on PI Pages, $1.9B a year on research, 803 research doctorates a year.
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