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Dino Di Carlo: Some T Cells Could Make Them Universal Cancer Killers

healthsciences.ucla.edu

Aug 12, 2025, 22:18

Dino Di Carlo: Some T Cells Could Make Them Universal Cancer Killers

Dino Di Carlo, Chair at UCLA Department of Bioengineering, shared a post on LinkedIn:

“Some T cells play by a different rulebook—and it could make them universal cancer killers.

In our new preprint, we show how to find and rank these rare T cells by directly linking their genetic code (TCR sequence) to secretions important for their cancer-killing function. Using our nanovial platform, we pulled cells straight from blood, measured their functional response, and recovered new receptors that were all active in tumor-killing tests—including in vivo models.

These aren’t your typical protein-recognizing T cells. Instead, subsets of these “unconventional T cells” like MAIT and iNKT cells detect metabolites and lipids—chemical products of cellular metabolism—presented by special MHC-like molecules (MR1 and CD1d). That means they can sense the metabolic fingerprints of life processes gone wrong, from infections to cancer. And because their recognition is not limited by HLA type, they could form the basis of “off-the-shelf” engineered T cell therapies that work for far more patients.

We are excited by this new approach because it’s simple to adopt and provides actionable insights in the first screen. Any lab can use nanovials, along with commercial flow sorters and single-cell sequencing instruments, to discover and rank their own TCRs, whether from unconventional metabolite- or lipid-recognizing T cells (using MR1- and CD1d- coated nanovials), or from conventional peptide-recognizing T cells (using peptide-MHC-coated nanovials). By linking sequence to function right from the start, you can zero in on the receptors most likely to work in vivo and the clinic.

Many thanks to Citra Soemardy, Charlie Li, Yichen Zhu, and Lili Yang. Please keep an eye out for Lili’s work on leveraging unconventional T cells as new therapeutics in the coming years. Many thanks for the support of the Chan Zuckerberg Initiative Exploratory Cell Network Program ( Norbert Tavares, Ph.D.).

Talk to us, or reach out to Partillion Bioscience who makes nanovials commercially, if this is something you are interested in using for your research projects.”

Title: A Nanovial-Based Platform for Functional Discovery of Antigen-Reactive TCRs from Unconventional T Cells

Authors: Citradewi Soemardy, Yan-Ruide Li, Yichen Zhu, Lili Yang, Dino Di Carlo

Read the Full Article.

Dino Di Carlo

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