# Novel Mechano-Acoustic Enhancement of Immunotherapy

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $109,439

## Abstract

PROJECT SUMMARY/ABSTRACT
Despite the unprecedented effects of immunotherapy in treating cancer, over 50–80% of patients will not
respond to treatment and will endure severe adverse and life-threatening events due to treatment. Approaches
to sensitize tumors to immunotherapy are urgently being explored. One very promising approach is the use of
radiation therapy due to known immunomodulating effects. Another promising approach is to target tumor
endothelial cells with pharmaceuticals to minimize their immunosuppressive properties. In normal tissues,
endothelial cells act as a regulating gateway for the immune system. In cancer, endothelial cells are highly
abnormal and immunosuppressive. We propose to explore novel approaches to enhance tumor
immunogenicity by mechanical targeting of tumor endothelial cells. This goes beyond pharmaceutical targeting
localizing the treatment and minimizing systemic effects or adverse events. Our previous research
demonstrated that ultrasound-stimulated microbubbles (USMB) can activate mechanotransduction pathways in
tumor endothelial cells through mechano-acoustic forces, which in turn significantly enhance radiotherapy.
Given that endothelial immunogenicity is known to be directly affected by mechanical forces, and that radiation
is a known immunomodulator, we posit that USMB treatments can enhance the effects of immunotherapeutic
strategies that may include radiation. Our proposed research includes: i) characterization of tumor endothelium
immunogenicity resulting from mechanical forces, and ii) pre-clinical assessment of combined treatment
regimens that include USMB, immunotherapy and/or radiation. Through this work, we will also gain a deeper
understanding of the role of endothelial cells in immunotherapy, and whether mechanical forces can alter
endothelial surface marker expression and general immunogenicity. Equipped with this research, our goal will
be to initiate a larger research program designed to introduce mechano-acoustic forces for immunomodulation
in cancer and in other immune-based diseases, and to study these effects in more advanced and clinically-
relevant biological models.
past year. In addition, as

## Key facts

- **NIH application ID:** 11062045
- **Project number:** 7R21CA256708-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Ahmed El Kaffas
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $109,439
- **Award type:** 7
- **Project period:** 2022-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11062045

## Citation

> US National Institutes of Health, RePORTER application 11062045, Novel Mechano-Acoustic Enhancement of Immunotherapy (7R21CA256708-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11062045. Licensed CC0.

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