# Biomaterials-based metabolic rescue of dendritic cells for vaccine design

> **NIH NIH R01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2022 · $324,766

## Abstract

Abstract
The main goal of this proposal is to develop biomaterial-based technologies that can modulate the functions of
DCs and T-cells in the draining lymph nodes in the presence of systemically delivered metabolic inhibitors. The
hypothesis of this proposal is that polymeric biomaterials-based particles generated from central-carbon
metabolites (targeting DCs via phagocytosis) can restart glycolysis/TCA cycle in DCs in the presence of
metabolic inhibitors and will also induce robust vaccine responses in immunocompetent mice. Notably, we
have generated polymers of central-carbon metabolites from glycolysis and TCA cycle, which were able to
activate DCs even in the presence of metabolic inhibitors. Moreover, these particles were able to rescue the
metabolic inhibition, as observed by up-regulated extracellular acidification rate (ECAR) and oxygen
consumption rate (OCR) in bone marrow derived DCs. In vivo PEGS particle formulations delivering TRP-2
peptide (without any adjuvant), were able to prevent the growth of subcutaneous B16F10 tumors in the
presence of CB-839 a glutaminase inhibitor. Similarly, F16BP vaccine particles delivering TRP2 peptide
antigen along with poly(I:C) as adjuvant and PFK15, a glycolytic inhibitor, were able to reverse the growth of
subcutaneous YUMM1.1 tumors. The hypothesis of this proposal will be tested using the following specific
aims: Aim 1: Evaluate if F16BP particles induce antigen-specific long-term memory T cell responses in
immunocompetent mice in the presence of glycolytic inhibitor PFK15. Aim 2: Determine if PEGS particles can
induce antigen-specific long-term T cell responses in immunocompetent mice in the presence of glutaminase
inhibitor CB-839. Aim 3: Determine toxicity profile and maximum tolerable doses of vaccines. The results
obtained from these experiments will shed light on the effect of metabolic reprogramming on the efficacy of
vaccine therapy.

## Key facts

- **NIH application ID:** 10322658
- **Project number:** 5R01AI155907-02
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Abhinav Acharya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $324,766
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322658

## Citation

> US National Institutes of Health, RePORTER application 10322658, Biomaterials-based metabolic rescue of dendritic cells for vaccine design (5R01AI155907-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10322658. Licensed CC0.

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