# Lab on a particle technology for functional screening of therapeutic cells

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $263,241

## Abstract

SUMMARY/ABSTRACT
Engineered cell therapies have become a cornerstone of medicine, along with molecular (drugs and proteins)
and genetic (gene therapy) interventions. However, new tools are needed to select, analyze, and design these
“living drugs”. In the last few years, there has been particular success in the use of engineered immune cell-
based therapies in treating hematologic malignancies, including recent FDA approvals of two chimeric antigen
receptor (CAR)-T-cell products. Unfortunately, this success has not translated broadly, for example, to more
prevalent solid tumors. One of the challenges in optimizing these therapies is that, unlike molecular therapies in
which structure and function are intimately linked, cellular therapies are more difficult to functionally design, as
conventional classifications of cells based on surface marker expression or target antigen affinity are poorly
correlated with anti-cancer functions, such as cytokine secretion and cell killing. In fact, recent single-cell screens
have highlighted an astonishingly high level of functional diversity from T-cells isolated from the same patient
and bearing the same panel of surface markers, with only a small highly active subset of cells driving responses
to immunological challenge.
Various single-cell functional profiling platforms have emerged over the past several years, but their widespread
adoption has been limited due to low assay throughputs, high-costs, or the need for skilled operators and
expensive customized instrumentation. Broadly accessible technologies are needed to uncover the links
between T-cell molecular and functional properties and anti-cancer activity, and ultimately, to enable the
production and selection of the most efficacious cell therapies. We propose the development of a novel “lab on
a particle” platform, which allows the rapid isolation of individual T-cells into uniformly sized nano-droplets, each
formed by a microparticle with a structured cavity (termed a nanovial). This approach will provide simultaneous
measures of both cell surface and secreted proteins, and recover cells with desired phenotypes at high rates
using standard fluorescence-activated cell sorting (FACS) machines. Importantly, no knowledge of microfluidics
or other specialized techniques is required to use nanovials. Our aims focus on: (1) developing nanovials with
optimal adhesive properties for T-cell attachment and compatibility with a broad range of FACS instruments; and
(2) sorting and characterizing individual antigen-specific T-cells based on interleukin-2 (IL-2) and interferon-γ
(IFN-γ) production. We will test the hypothesis that T-cells sorted based on production of IL-2 and IFN-γ, as
measured in nanovials, will have improved effector function. Our new technology promises to remove a
significant barrier to entry in functional immune cell selection, and drive next-generation cancer
immunotherapeutic design.

## Key facts

- **NIH application ID:** 10272940
- **Project number:** 1R21CA256084-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Dino Di Carlo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $263,241
- **Award type:** 1
- **Project period:** 2021-09-09 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10272940

## Citation

> US National Institutes of Health, RePORTER application 10272940, Lab on a particle technology for functional screening of therapeutic cells (1R21CA256084-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10272940. Licensed CC0.

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