# Photothermal Nanoparticles Immune Engineer Tumor-specific T cells for Adoptive Cell Therapy

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2024 · $598,805

## Abstract

PROJECT SUMMARY
This goal of this proposal is to investigate a novel photothermal nanoparticle-based approach for generating
tumor-specific T cells as an adoptive T cell therapy (ATCT) for glioblastoma (GBM). Despite being the most
commonly diagnosed brain tumor, the prognosis for GBM patients is dismal, with a relative five-year survival rate
of 7.5%. Hence, there is an urgent need for novel therapies for this patient population. In response, we are
synthesizing novel Prussian blue nanoparticle-based formulations that will be used to administer photothermal
therapy (PBNP-PTT) and generate a personalized ATCT for GBM. Our approach involves treating GBM tumor
cells resected during surgery with PBNP-PTT ex vivo, and co-culturing them with dendritic cells (DCs) and T
cells expanded from PBMCs sourced from the patient or a matched donor, to expand GBM-specific T cells for
subsequent ATCT. We envision our therapy to be administered to patients after standard-of-care regimens of
surgery, chemotherapy, and radiation therapy, when GBM patients are in a minimally residual disease state, with
the goal of maximizing the impact of the T cell therapy thus improving survival outcomes. In a recently published
study with GBM tumor cell lines, we demonstrated that PBNP-PTT generated more potent tumor-specific T cells
in terms of specificity and cytolytic function, when compared to T cells generated by freeze-thaw lysis of the GBM
tumor cells or by heating of the tumor cells on a heat block at equivalent thermal doses. In vivo, our immune
engineered T cells eliminated orthotopically implanted U87 xenograft tumors and significantly improved survival
compared to tumor-bearing animals treated with lysate-derived, antigen (PRAME)-specific, or PHA-expanded T
cells, and control treatments. Operationally, our approach represents a more seamless workflow than other
personalized approaches. It involves a straightforward, single administration of PBNP-PTT to the GBM cells
isolated after surgery for 10 minutes using PBNPs pre-synthesized with GLP techniques and a portable laser,
followed by well-established DC and T cell expansion protocols. Building on these promising findings, we now
propose to synthesize multiple PBNP-PTT nanoformulations to generate and expand tumor-specific T cells and
conduct studies testing their efficacy in vitro, in vivo, and ex vivo, as well as mechanistic studies. We hypothesize
that PBNP-PTT of GBM tumor cells using our PBNP nanoformulations significantly enhances antigen release
and capture by the PBNPs, their processing and presentation by DCs allowing more robust activation of a diverse
T cell population, which subsequently differentiates into cytotoxic effector and long-lasting memory phenotypes,
the ideal ATCT product for safe and effective treatment of GBM. Success in this project will demonstrate the use
of PBNP-PTT nanoformulations to generate a transformative, new class of ATCT for GBM.

## Key facts

- **NIH application ID:** 10869504
- **Project number:** 1R01CA290045-01
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Conrad Russell Young Cruz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $598,805
- **Award type:** 1
- **Project period:** 2024-04-03 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869504

## Citation

> US National Institutes of Health, RePORTER application 10869504, Photothermal Nanoparticles Immune Engineer Tumor-specific T cells for Adoptive Cell Therapy (1R01CA290045-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10869504. Licensed CC0.

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