# Engineered Glioblastoma Tumor Immunity for Personalized Immunotherapy

> **NIH NIH R21** · NEW YORK UNIVERSITY · 2020 · $191,878

## Abstract

PROJECT SUMMARY
Engineered Glioblastoma Tumor Immunity for Personalized Immunotherapy
Glioblastoma (GBM) is the most common, malignant primary adult brain tumor and patients succumb to
relapse despite aggressive regimens of surgery, chemotherapy and radiotherapy. PD-1 immune checkpoint
blockades are considered promising avenues in GBM clinical trials by empowering pre-existing patient
immunity against malignant GBM tumors. However, there are no accurate biomarkers to stratify responders
and nonresponders and reliable approach to evaluate PD-1 immunotherapy efficacy. Despite promising clinical
trial results, a prolonged challenge in GBM immunotherapies is suboptimal responses and frequent resistance
to PD-1 immune checkpoint blockades. Traditional patient-derived xenografts, patient explant cultures, and in
vitro dissociated cell cultures all fail to predict patient responses and expose therapeutic resistance
mechanisms, because they do not accurately reconstitute GBM pathology: tumor-immune-vascular interactions,
altered cell-ECM interactions, elevated hypoxic and interstitial fluid pressure. In this study, we surpass such
discrepancies by integrating notable hallmarks of the interactive GBM tumor microenvironment in an ex vivo
organotypic system consist of diffuse tumor-associated macrophage (TAMs) and T-lymphocyte infiltration and
immunosuppression, GBM-associated microvascular angiogenesis, elevated hypoxic and interstitial fluid
pressure. Simultaneously, we will monitor in situ inflammatory cytokine secretions of patient immunity during
real-time GBM tumor immunosuppression and immunotherapy.
 The objective of this research is to engineer a novel, microfluidics-based, integrated, tunable ‘Glioma-on-
a-Chip’ organotypic model that recapitulates the in vivo brain tumor microenvironment and immunity for a
multiparametric analysis of GBM interactions during PD-1 immunotherapy. We aim to optimize immune
checkpoint blockade efficacy using our ex vivo ‘Glioma-on-a-chip’ that integrates controllable intercellular
interactions (patient-derived GBM and endothelial cell spheroids, TAMs and T cells), tunable matrix mechanics
(alterable intercellular and extracellular adhesive signatures, matrix stiffness), controllable extracellular
dynamics (on-chip hypoxia and interstitial fluid pressure regulators) and measurable immunosuppressive
conditions (on-chip nanoplasmonic biosensing for real-time mapping of patient immune responses under GBM
immunosuppression and immunotherapy). Our tunable and multifunctional microsystem allows us to probe the
dynamic tumor immunity and unravel a crosstalk mechanism for immunotherapeutic resistance. We propose a
new brain cancer immunotherapeutic strategy of “hacking” the immunosuppressive GBM niche to co-target
tumor angiogenesis and immune checkpoints for effectively combating GBM. This may significantly accelerate
the pace for identifying immune checkpoint biomarkers, developing patient-specific immunotherapeutic
strategi...

## Key facts

- **NIH application ID:** 9948650
- **Project number:** 5R21EB025406-03
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Weiqiang Chen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,878
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948650

## Citation

> US National Institutes of Health, RePORTER application 9948650, Engineered Glioblastoma Tumor Immunity for Personalized Immunotherapy (5R21EB025406-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948650. Licensed CC0.

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