# Tri-Signal Artificial Antigen Presenting Cells for Cancer Immunotherapy

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2024 · $48,974

## Abstract

PROJECT SUMMARY
 Adoptive cellular therapy (ACT) treatments, in which cancer patients are infused with autologous tumor-
specific cytotoxic (CD8+) T cells expanded and activated ex vivo, have become gradually more appealing for
cancer patients. Although ACT has shown great clinical success with melanoma, universal adoption has been
limited, as ACT relies on extremely complex cell-based methods with a significant price tag. Recently, increased
emphasis has been placed on enhancing acellular platforms, such as artificial antigen presenting cells (aAPCs),
that show promise in activating tumor-specific CD8+ T cells in a quicker, more tunable manner. While a majority
of aAPC systems have been applied in ex vivo settings, the development of biocompatible materials for aAPC
platforms have expanded the potential of these systems to be used in vivo, lessening the lengthy culture times
and costs associated with therapy. The goal of the proposed project is to develop a novel biomaterial aAPC for
direct, antigen-specific activation of CD8+ T cells in vivo for cancer immunotherapy. The particulate platform is
made from a novel blend of biodegradable and biocompatible polymers, Poly(lactic-co-glycolic) acid (PLGA) and
Poly(beta amino ester) (PBAE), that promotes inclusion of the three signals required for optimal T cell activation
and expansion. We will investigate the effects of biomaterial properties and signal incorporation on in vitro T cell
activation, as well as gain insight into in vivo antigen-specific T cell activation in a tumor-burdened host.
We will develop immunologically compatible, particulate PLGA/PBAE aAPCs for in vivo injection and T
cell activation. First, we will investigate physicochemical properties of these aAPCs, including biomaterial
composition, size, and surface protein density. We will optimize these properties in the context of enhanced
CD8+ T cell activation and biological function. Second, we will focus on incorporating cytokines, additional signals
that are important in T cell activation, in a local and sustained manner. We will investigate various cytokines,
such as IL-2, IL-15, and IL-21, that may play a role in generating effector and memory T cells. Taken together,
we will identify leading tri-signal aAPCs that are optimized for both murine and human T cell activation in vitro.
Finally, we will apply our leading aAPCs in vivo, to analyze their CD8+ T cell activation, expansion, and anti-
tumor capacities. If successful, this proposal will generate a novel biomimetic approach for harnessing optimal
antigen-specific CD8+ T cell responses, with the potential of expanding patient access to cancer
immunotherapies and reducing health disparities.

## Key facts

- **NIH application ID:** 10913348
- **Project number:** 5F31CA284859-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Sydney Rose Shannon
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913348

## Citation

> US National Institutes of Health, RePORTER application 10913348, Tri-Signal Artificial Antigen Presenting Cells for Cancer Immunotherapy (5F31CA284859-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10913348. Licensed CC0.

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