Theodore Nowicki
University of California-Los Angeles, CA·Microbiology & Immunology
One way to treat cancer is to engineer a patient's own T cells, immune cells that recognize and kill infected or abnormal cells, so that they target a tumor. The T cells are given either a transgenic T-cell receptor (TCR) or a chimeric antigen receptor (CAR), each of which lets them recognize a marker on cancer cells.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Biomedical Engineering
- Topics
cancer immunotherapy
adoptive cell therapy
CAR-T cells
- Grants
- 1 known grant, through Feb 2030
What they work on
- Compare TNF-alpha-armed and conventional TCR and CAR T cells in humanized mouse xenografts, testing tumor killing, toxicity and T-cell entry into tumors across several TCRs, CARs and tumor types.
- Map how added TNF-alpha changes gene and protein activity inside tumors, using spatial transcriptomics and proteomics on tumor tissue from treated humanized mice.
- Profile tumor-infiltrating T cells from these mice with mass cytometry, single-cell cytokine secretion assays and single-cell phospho-proteomics to define how TNF-alpha changes T-cell function under chronic stimulation.
- Test whether TNF-alpha acts through TNF receptor 2 (TNFR2) to block Th2 immunosuppressive activity, using repeated tumor-stimulation assays and TNFR2 knockout T cells.
More about the research
These therapies can work dramatically against some solid tumors, but many patients do not respond. The team has previously shown that patients whose engineered T cells secrete more tumor necrosis factor alpha (TNF-alpha), an inflammatory signaling protein, respond better. They have also shown that TNF-alpha dampens T helper 2 (Th2) cells, a type of immune cell that suppresses tumor-killing responses.
Why it matters
Patients with solid tumors who do not respond to TCR or CAR T-cell therapy, or who relapse after treatment, could benefit if adding TNF-alpha makes engineered T cells more effective without more toxicity. The work could support moving TNF-alpha-armed T cells toward next-generation cell therapies. It may also clarify how TNF-alpha shapes T-cell behavior during long-term exposure to tumors.
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.
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.
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.
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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