# Nano Immune-Imaging Core

> **NIH NIH P01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $174,026

## Abstract

CORE B - SUMMARY/ABSTRACT
Lymph nodes (LNs) play a pivotal role in regulating alloimmune responses. The overall goals of this core are (i)
to develop innovative nanodelivery strategies to reprogram the stroma of aged LNs and (ii) to carry out advanced
immune imaging for the homing of aged immune cells to the LNs and their interactions within the LNs. Targeted
delivery of therapeutics to the LN and reprogramming of its stroma would not only inhibit the priming of
alloreactive T cells, but also antagonize memory T cells. Central memory T cells require less stringent activation
stimuli to generate vigorous immune responses. Since memory T cells represent the main barriers to tolerance
induction, therapeutic strategies that specifically target memory T cells address a high unmet need in heart
transplantation. On the other hand, LNs become the primary sites of Treg formation when tolerogenic therapies
are used. The main goal of Core B is to establish a method of targeted delivery of immune therapeutics to the
LN to facilitate transplant tolerance by reprogramming the LN stroma. Core B will be responsible for the
nanoformulation of immune therapeutics proposed in these projects. Core B will also fully characterize these
nanoproducts regarding important parameters such as size, shape, charge, stability and release kinetics.
Nanomedicine has great potential for developing site-specific targeted delivery of therapeutics. We are using a
well-defined, specific delivery strategy that targets glycoprotein molecules known as peripheral node addressin
(PNAd), expressed by very specialized veins present exclusively in the LNs, referred to as high endothelial
venules (HEVs). Core B will be generating nanoparticles (NPs) encapsulated with various payloads and coated
with MECA-79 mAb, which recognizes PNAd molecules on HEVs. The overall hypothesis of Core B is that
targeted delivery of immune therapeutics to LNs via HEVs permits specific deposition of payloads to the LNs,
with the ultimate goals of suppressing alloreactive T cells and promoting graft acceptance. On the other hand,
advanced immune imaging of LNs can provide unparalleled information on the trafficking properties of aged
immune cells across aged HEVs. These studies can also comprehensively assess their live interactions within
the aged LNs. In addition, these advanced imaging studies of LNs can provide novel information on the impact
of therapeutics used in this project on immune cell homing and their interactions within the LNs. Therefore, Core
B will have two aims: (i) targeted nanodelivery of therapeutics to aged LNs and (ii) advanced live immune imaging
of LNs for immune cell and NP trafficking.

## Key facts

- **NIH application ID:** 10862422
- **Project number:** 1P01AI175397-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Reza Abdi
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $174,026
- **Award type:** 1
- **Project period:** 2024-05-03 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862422

## Citation

> US National Institutes of Health, RePORTER application 10862422, Nano Immune-Imaging Core (1P01AI175397-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10862422. Licensed CC0.

---

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