# Engineering injectable T cell stimulating microparticles for cancer immunotherapy

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2022 · $46,752

## Abstract

Project Summary
 Adoptive T cell therapy (ACT) is a T cell based cancer therapy in which autologous T
cells are isolated from the patient, activated and expanded ex vivo, then reinfused into the
patient. While ACT has shown great clinical success, the success has been limited to
melanoma, and complex manufacturing considerations create a large price tag. Innovations in in
scalable, acellular systems for T cell activation, such as artificial antigen presenting cells
(aAPCs), has improved the ex vivo expansion of CD8+ T cells by shortening culture times and
providing tighter control of the resulting T cell phenotype and function. However, T cell culture
with aAPCs still takes several weeks and requires manufacturing labor and cost. Platforms for in
vivo activation of antigen-specific T cells would decrease the cost and complexity of T cell
therapy. The goal of the proposed project is to create the first biomaterial scaffold for direct, in
vivo, antigen-specific activation of CD8+ T cells for cancer immunotherapy. The platform,
termed the artificial lymph node (aLN), is a hyaluronic acid hydrogel conjugated with signals 1
(peptide-MHC), 2 (anti-CD28) and 3 (cytokine support) that can be injected subcutaneously to
create a T cell activating microenvironment. We will investigate the effects of 3D scaffold
parameters on T cell activation as well as gain insight into the dynamics of in vivo antigen-
specific T cell activation in an immune competent host.
 We will develop injectable aLN microparticles (MPs) that will compact in vivo to form a T
cell activating scaffold. We will first investigate physical properties of the aLN MPs such as
signal density, stiffness, and size. We will also investigate the addition of cell adhesion proteins
to facilitate migration of the T cells within the scaffold. Second, we will incorporate a local and
sustained signal 3 (cytokine) signaling component. We will test a variety of cytokines, including
IL-2, IL-7, IL-15, and IL-21, for their ability to generate both effector and memory cells. With the
lead cytokine cocktail, we will test two methods of integration, antibody presentation and
encapsulation. These aLN parameters will be optimized for both murine and human antigen-
specific T cell expansion. Finally, we will test the efficacy of the aLN MPs for in vivo activation
and expansion of CD8+ T cells and their anti-cancer efficacy, using B16-OVA, B16-SIY, and
MC38-OVA for mouse T cells, and the human SK-MEL-37 (A2+/NY-ESO-1+) melanoma cell
line for human T cells. If successful, this proposal will produce a novel acellular approach for the
in situ generation of an antigen-specific T cell response, expanding the access of
immunotherapy to more patients.

## Key facts

- **NIH application ID:** 10537258
- **Project number:** 1F31CA275271-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Natalie Katerina Livingston
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537258

## Citation

> US National Institutes of Health, RePORTER application 10537258, Engineering injectable T cell stimulating microparticles for cancer immunotherapy (1F31CA275271-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10537258. Licensed CC0.

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