# Scaffolds mimicking antigen presenting cells

> **NIH FDA R01** · HARVARD UNIVERSITY · 2020 · $600,000

## Abstract

Current approaches to expand T cells ex vivo for therapeutic applications are limited by low expansion rates
and T-cell products of limited functionality. To address these issues, we have recently described a system that
mimics natural antigen-presenting cells (APCs). These APC-mimetic scaffolds (APC-ms) consist of a fluid lipid
bilayer supported by mesoporous silica micro-rods (MSRs). The lipid bilayer presents membrane-bound cues
for T-cell receptor stimulation and costimulation at predefined densities, while the micro-rods enable sustained
release of soluble paracrine cues. Using anti-CD3, anti-CD28 and controlled release of interleukin-2, we have
shown that the APC-ms promotes ten-fold greater polyclonal expansion of primary mouse and human T cells
than commercial beads (Dynabeads), and can be used to tune the phenotypic attributes of expanded T-cell
products. APC-ms also support over 5-fold greater expansion of CD19 CAR-T cells than Dynabeads, with
increased efficacy in a clinically-relevant xenograft lymphoma model. While APC-ms is a promising T cell
expansion system, there are several development activities that would aid its clinical and commercial
translation. The current MSR synthesis process has not been standardized for this application, and lacks
established SOPs to yield material products with consistent properties. Currently, surface cues are presented
on APC-ms using biotin-streptavidin, but the use of click chemistry in place of streptavidin could provide a
number of advantages. While APC-ms is designed to completely degrade during the process of T cell culture
period, obviating the need for its removal before cell delivery, we have not yet thoroughly explored the impact
of any potential residual materials on the infused T cell products. These needs lead to the following specific
objectives for this project (1) Establish SOPs for APC-ms synthesis. This will include identifying MSR critical
quality attributes (CQAs) for functional APC-ms and understanding how critical process parameters (CPPs) in
MSR synthesis affect those CQAs (2) Develop a process to directly and selectively conjugate surface cues
onto lipid bilayers, via click chemistry, to simplify and modularity of APC-ms assembly and function. (3)
Characterize residual APC-ms materials during T cell processing, and perform a thorough in vivo safety
assessment. The successful achievement of these aims will immediately address key issues related to using
APC-ms as an ex vivo T-cell expansion platform.

## Key facts

- **NIH application ID:** 10001355
- **Project number:** 5R01FD006589-03
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** David J Mooney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2020
- **Award amount:** $600,000
- **Award type:** 5
- **Project period:** 2018-09-20 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001355

## Citation

> US National Institutes of Health, RePORTER application 10001355, Scaffolds mimicking antigen presenting cells (5R01FD006589-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001355. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*