# Engineered Glioblastoma-specific T cells using Immunostimulatory Photothermal Nanoparticles

> **NIH NIH R41** · IMMUNOBLUE, LLC · 2024 · $399,669

## Abstract

PROJECT SUMMARY
The goal of this STTR Phase I application is to establish the feasibility of commercializing a personalized and
multi-targeted adoptive T cell therapy (ATCT) for glioblastoma (GBM). GBM is the most common primary brain
tumor with a dismal prognosis and relative five-year survival rate of 7.5%. There has been no significant
improvement in outcomes for these patients in two decades. In response to this urgent need for novel
therapies for GBM patients, we have developed a personalized, autologous ATCT targeting multiple antigens
in GBM unique to each patient. We envision administering the ATCT as an adjuvant therapy directly into the
tumor bed through an Ommaya reservoir after standard-of-care surgery. Our strategy for generating a GBM-
specific ATCT involves applying Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) to GBM
cells ex vivo. During PBNP-PTT, PBNPs are administered to GBM cells that have been excised via surgery,
and a near infrared laser is shone onto the mixture ex vivo, thereby generating heat. Under certain conditions,
PBNP-PTT delivers a thermal dose that elicits immunogenic cell death (ICD) in GBM cells and facilitates the
release of GBM-specific antigens unique to each patient. The PBNP-PTT-treated GBM cells are then co-
cultured with autologous dendritic cells (DCs) and T cells, to expand GBM-specific T cells for subsequent
infusion back into the patient. Importantly, this platform is designed to develop multi-targeted T cells in an
antigen-agnostic manner. Since this approach uses a patient’s own tumor as the source of T cell targets, it
does not require a priori chosen antigens. Our published data illustrates the feasibility of our novel ATCT
development platform using PBNP-PTT to generate potent and functional GBM-specific T cells against two
GBM cell lines, U87 and SNB19, using healthy donor PBMCs HLA-matched to the tumor cell lines. In another
published study using an orthotopic U87 xenograft model, we have demonstrated that our ATCT is more
effective in generating in vivo tumor regression and long-term survival relative to alternative and control
ATCTs. Building on these published results, in this STTR Phase I study, we seek to establish the feasibility of
developing autologous GBM-specific T cells with our PBNP-PTT-based platform using blood and GBM tumor
samples from patients. Our overall hypothesis is that PBNP-PTT-treated GBM cells facilitate the generation of
potent and personalized GBM-specific T cells in an antigen-agnostic manner that exert specific cytotoxicity
against autologous patient-derived GBM cells in vitro and in vivo. In Aim 1, we evaluate whether PBNP-PTT-
mediated ex vivo expansion generates potent and effective patient-derived GBM-specific T cells and define the
mechanisms driving the observed responses. In Aim 2, we test the efficacy of the PBNP-PTT-derived T cells in
GBM patient-derived xenograft (PDX) models in vivo compared to other T cell approaches (e.g. B7-H3 CAR T...

## Key facts

- **NIH application ID:** 11002528
- **Project number:** 1R41CA287488-01A1
- **Recipient organization:** IMMUNOBLUE, LLC
- **Principal Investigator:** Rohan Fernandes
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,669
- **Award type:** 1
- **Project period:** 2024-09-03 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11002528

## Citation

> US National Institutes of Health, RePORTER application 11002528, Engineered Glioblastoma-specific T cells using Immunostimulatory Photothermal Nanoparticles (1R41CA287488-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11002528. Licensed CC0.

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