# Improving cell-based  immunotherapy for solid tumors using mechanical modulation

> **NIH NIH R01** · CORNELL UNIVERSITY · 2024 · $83,230

## Abstract

Project summary
Cell-based immunotherapy such as chimeric antigen receptor (CAR)-T and CAR-natural
killer (NK) cells have shown tremendous successes in hematomalignancies. However, it
has had limited positive outcomes in the treatment of solid tumors. For effective killing of
tumor cells, immune cells must be physically engaged with the tumor cells and form an
immunological synapse. In solid tumors, a main challenge is for the immune cells to
infiltrate to the tumor core and to physically surround each tumor cells. Here, we
hypothesize that mechanical stresses within the target tumor critically regulate the
immune cell infiltration into the tumor core, as well as their ability to form immunological
synapse with tumor cells. As such, mechanical stresses can be utilized to improve
immune cells’ ability to kill tumor cells. To test this hypothesis, we propose the following
specific aims. Aim 1: We will determine roles of mechanical forces in regulating infiltration
of natural killer cells into the tumor spheroid core. Aim 2: We will determine roles of
mechanical compression in potentiating tumor spheroids for effective immune killing. We
will use a 3D microfluidic compression device developed under parent grant to control
mechanical stresses within the tumor spheroids. Natural killer cells and breast tumor
spheroids embedded within a collagen matrix will be used to recreate the 3D tumor
microenvironment. The proposed project extends the current mechano-immune
regulation assay from a 2D to 3D platform. The delivery of this research project will be a
set of mechanical conditions, extracellular matrix architecture, compression rate and
frequencies for effective tumor killing. These results can be used to guide future CAR-
NK cell based immunotherapies for the treatment of solid tumors. An equally important
component of this project is to provide a training opportunity for a first year URM graduate
student to set a solid foundation for a PhD thesis program, and also to enable her to reach
a personal goal of supporting the educational advancement of underrepresented
communities.

## Key facts

- **NIH application ID:** 11061137
- **Project number:** 3R01CA221346-07S1
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Mingming Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $83,230
- **Award type:** 3
- **Project period:** 2017-08-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11061137

## Citation

> US National Institutes of Health, RePORTER application 11061137, Improving cell-based  immunotherapy for solid tumors using mechanical modulation (3R01CA221346-07S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11061137. Licensed CC0.

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