# Microphysiological platform for analyzing multiple myeloma's tumor microenvironment, enabling immunotherapy assessment and drug screening.

> **NIH NIH R33** · NORTHEASTERN UNIVERSITY · 2024 · $427,095

## Abstract

ABSTRACT
 The tumor microenvironment (TME) plays a critical role in hematologic malignancies, especially in
multiple myeloma (MM). Each cellular and non-cellular component of the TME exerts a different effect on MM
cell survival, proliferation, immune evasion, and resistance to treatment. Several studies have shown that CAR-
T therapy produces an overall response rate of 78% in the relapsed/refractory MM setting; however, many
patients still relapse, and the median time to disease progression is about 1 year. Therefore, there is an urgent
need to define mechanisms of disease progression and resistance to CAR-T and bispecific antibodies using an
in vitro cell culture system that mimics the complex TME.
 Continuous progress in tissue engineering, including the development of various 3D scaffolds and
microfluidic systems, has improved the diversity, fidelity, and capacity of culture models that can be used in
cancer and other disease research. Most 3D in vitro culture systems lack the integral TME and dynamic perfusion
and/or influence immune-tumor crosstalk or/and prolonged culture capabilities. In addition, most models cannot
mimic the hypoxic gradients observed in tumors, which dramatically reduces the efficacy of molecular and
cellular therapeutics. The hypoxic TME likely protects tumors against immunotherapies by altering cellular
metabolism and inducing immune suppression. Therefore, an ideal experimental in vitro cell culture system
should mimic the heterogeneous nature of the hypoxic TME to allow a more complete understanding of cancer
cell and immune cell biology, immunotherapy validation, and development of efficacious treatment strategies for
clinical application. To address the aforementioned limitations, in this proposal, we will focus on developing a
novel microfluidic droplet-based platform (MDP) technology to generate and analyze a 3D biomimetic
multicellular immunogenic tumor model and test its capabilities to (1) establish multiple levels of hypoxia within
the same tumor-chip for parallel processing; (2) investigate spatiotemporal interaction between TME cancer-
immune cells during therapy; (3) quantify the impact of state-of-the-art targeted immunotherapy efficacy and
define multiparametric (dynamic, secretomic, and transcriptomic) responses for a comprehensive analysis of cell
fate. We will incorporate patient tumor cells and their microenvironment in MDP to predict the status of the patient
as a potential responder or non-responder. Potential responders to immunologic therapy such as CAR-T will
benefit from not having to wait for several months in clinic to determine whether the therapy has achieved
response or not, while potential non-responders will be spared the side-effects of non-effective treatment and
help clinicians choose other forms of therapy. Our approach will therefore result in the development of a versatile
and multifunctional system that can serve as a new and innovative technology for deep analysis of cell-cell
...

## Key facts

- **NIH application ID:** 10916687
- **Project number:** 1R33CA291125-01
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** Tania Tali Konry
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $427,095
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10916687

## Citation

> US National Institutes of Health, RePORTER application 10916687, Microphysiological platform for analyzing multiple myeloma's tumor microenvironment, enabling immunotherapy assessment and drug screening. (1R33CA291125-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10916687. Licensed CC0.

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