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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...

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Ultrasound priming gated by solid tumor hallmarks to guide CAR-T therapy.

Tianze Guo1, Ziyue Zhu1, Yunjia Qu2

  • 1Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.

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|June 10, 2026
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Researchers developed SHIFTERS, a system using focused ultrasound to control CAR-T therapy for solid tumors. This enhances precision by targeting cancer hallmarks, improving treatment efficacy.

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Area of Science:

  • Biomedical Engineering
  • Cancer Therapy
  • Molecular Engineering

Background:

  • Chimeric antigen receptor T-cell (CAR-T) therapy shows high efficacy in hematologic malignancies.
  • CAR-T therapy faces significant challenges in treating solid tumors due to tumor heterogeneity and lack of specific targets.

Purpose of the Study:

  • To develop a novel system, SHIFTERS (solid-tumor hallmark inducible, focused-ultrasound triggered enhanced reprogramming system), for precise CAR-T cell activation in solid tumors.
  • To enable localized and tumor-specific antigen expression for enhanced CAR-T therapy efficacy.

Main Methods:

  • Designed an AND-gated circuit (SHIFTERS) using split transcription factors regulated by hypoxia-responsive and focused-ultrasound (FUS)-inducible promoters.
  • Engineered SHIFTERS to induce expression of the CD19 antigen specifically in FUS-sonicated, hallmark-positive tumor regions.
  • Tested the system in 3D spheroid and in vivo models with CD19 synNotch CAR-T cells.

Main Results:

  • SHIFTERS achieved robust, sustained, and localized CD19 expression in target tumor areas.
  • Hypoxia-gated SHIFTERS combined with synNotch CAR-T cells demonstrated significant tumor suppression in models.
  • The system successfully activated and trained CAR-T cells in a FUS-guided, localized manner.

Conclusions:

  • SHIFTERS provides a modular and ultrasound-controllable platform for CAR-T therapy in solid tumors.
  • This approach improves the precision and efficacy of CAR-T therapy by targeting tumor hallmarks and enabling spatial control.
  • The modularity allows adaptation to different tumor types, such as hepatocellular carcinoma using enAFP promoters.