Researchers Explore New Immunotherapy Method for Glioblastoma

Understanding Glioblastoma

Glioblastoma is the most prevalent and aggressive form of brain cancer, with patients typically surviving only about 14 months post-diagnosis and treatment. While immunotherapy has shown success in treating other cancers, it has not been effective for glioblastoma. Research indicates this may be due to a “cold” tumor microenvironment that lacks the immune cells necessary for immunotherapy to function effectively against cancer cells.

Transforming the Tumor Microenvironment

Researchers are working to convert the “cold” microenvironment into a “hot” one to enhance the effectiveness of immunotherapies, such as checkpoint blockade using anti-PD1 antibodies. Various methods exist to achieve this transformation, but side effects often limit their application. For instance, radiotherapy has demonstrated efficacy in reducing brain tumors in mice with the aid of radiation sensitizers and PD-1 blockade. However, the extent of X-ray exposure is restricted due to potential harm to healthy brain cells. Similarly, photodynamic therapy, although promising for breast cancer, is limited in glioblastoma due to penetration depth issues that vary by tissue type.

Innovative Approach Using High-Intensity Focused Ultrasound

A promising approach being investigated by researchers at the University of Minnesota involves using High-Intensity Focused Ultrasound (HIFU). Focused ultrasound therapies are generally safe and non-invasive, offering significant penetration depth. While thermal-based HIFU is already utilized for treating kidney tumors, it generates heat that can damage surrounding healthy tissues. Therefore, mechanical-based HIFU presents a potential alternative.

Study on Mechanical HIFU and Microshells

In a recent study, researchers assessed the effectiveness of mechanical HIFU combined with microshells filled with perfluorocarbon (PFC) to create a “hot” immune environment. This process involves injecting ultra-thin walled microshells containing PFC liquid into the tumor site. When mechanical HIFU is applied, the microshells rupture and disrupt nearby cancer cells, promoting the recruitment of immune cells and transforming the area into a “hot” immune environment. Under these conditions, the effectiveness of anti-PD1 immunotherapy significantly improved.

Comparative Analysis of HIFU Methods

The researchers compared mechanical HIFU with the thermal HIFU currently used in various cancer treatment protocols. In experiments conducted on mice, thermal HIFU raised surrounding temperatures by nearly 60 degrees Celsius, followed by a drop of 30 degrees, indicating complete microshell breakdown. In contrast, mechanical HIFU elevated the temperature by only seven degrees Celsius, with both methods achieving microshell rupture within two minutes.

Advantages of Direct Injection

Glioblastoma surgeries typically expose the brain, allowing for the direct injection of microshells in concentrated doses across the tumor area. The PFC inside the microshells enables visualization of the area using color Doppler imaging, facilitating precise guidance of HIFU. The researchers noted a strong survival curve in mice treated with mechanical HIFU in conjunction with anti-PD1 therapy, which presents encouraging results.

Future Implications

The findings suggest that the acoustic process of rupturing microshells with HIFU could accelerate immune pathway stimulation. This innovative method holds the potential to enhance existing immunotherapies for glioblastoma and other cancer types that may not respond to traditional checkpoint blockade treatments.

Written by Sameena Ahmed

References:
Wiley online library-Advanced therapeutics: Microshell Enhanced Acoustic Adjuvants for immunotherapy in Glioblastoma.
EurekAlert!: The ‘Goldilocks’ principle for curing brain cancer https://www.eurekalert.org/pub_releases/2019-10/uomm-tp100419.php
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