CarThera, a French company that designs and develops innovative ultrasound-based medical devices to treat brain disorders, today announces preclinical results in the testing of the combination of SonoCloud^® technology with immunotherapies.

This laboratory work was done in collaboration with Dr Amy Heimberger – a renowned expert in immunotherapies for glioblastoma (GBM) at the MD Anderson Cancer Center. The results were recently published online in the prestigious Clinical Cancer Research journal: ‘Opening of blood-brain barrier using low-intensity pulsed ultrasound (LIPU) enhances responses to immunotherapy in preclinical glioma models’.

In recent years, the use of immunotherapy has revolutionized the treatment of cancer; but these approaches have failed in multiple trials in GBM. The SonoCloud device uses LIPU to temporarily open the blood-brain barrier (BBB), and can enhance the delivery of various therapeutic approaches including CAR-T cells and checkpoint inhibitors to the tumor and surrounding brain parenchyma, for the treatment of glioblastoma and other brain tumors.

The positive results from this work pave the way for future clinical trials to test this approach. “Our studies clearly demonstrate that using pulsed ultrasound to temporarily disrupt the BBB can enhance the therapeutic effects of a variety of immunotherapeutic strategies for glioblastoma – by enhancing the delivery of antibodies, CAR-T cells and genetically-modified cellular immunotherapies to the tumor microenvironment – ultimately leading to better efficacy,” said Michael Canney, Scientific Director at CarThera.

Immunotherapy-based approaches also have the potential to generate long-lasting immunity in the brain – even beyond the treatment zone. “Our preclinical results indicate that the SonoCloud technology can markedly enhance and increase the efficacy of checkpoint inhibitors. This strategy demonstrated protection from subsequent tumor rechallenge in the untreated hemisphere,” said Dr Amy Heimberger, Professor of Neurosurgery and Scientific Director of Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center at Northwestern University, Chicago.

Immunotherapies are among the most important novel therapeutic advances in cancer treatment of the last decade; however they have not shown efficacy for primary brain tumors. Insufficient brain penetration may contribute to the disappointing results to date. The current preclinical results suggest an enhanced efficacy in combination with ultrasound-based blood-brain barrier opening, and support its use in human clinical trials. CarThera is presently exploring and testing the use of immunotherapies in patients with brain metastases from melanoma, in the SoniMEL study in Paris; similarly researchers from Northwestern University in Chicago are exploring the SonoCloud device in clinical trials for patients with GBM.