Treatment with Tumor Treating Fields triggers downstream anti-tumor cell response, study finds

Novocure announced that a new study published in the Journal of Clinical Investigation (JCI) finds treatment with Tumor Treating Fields (TTFields) mediated cell disruption activates the immune system and triggers an anti-tumor cell response that may be effectively used together with existing immunotherapy approaches in the treatment of solid tumors, with limited systemic toxicity.

TTFields' ability to activate a downstream immune response, effectively turning a cold tumor hot, is a unique element of TTFields therapy. Given the depth of clinical research focused on the use of immunotherapies and the broad applicability of TTFields, this could be critical to the treatment path for solid tumor cancers."

Uri Weinberg, Novocure's Chief Science Officer

Preclinical research has shown evidence that TTFields may induce a pro-inflammatory and broader immunological effect on tumor cells. This study outlines translational research by Dr. Dongjiang Chen and colleagues from the David Tran Laboratory of Quantitative Cancer Research at the University of Florida. Preclinical data demonstrated that treatment with TTFields directly disrupted the nuclear envelope of glioblastoma (GBM) tumor cells. This led to leakage of DNA that activates the cGAS/STING and AIM2 signaling pathways, driving early anti-tumor immune responses. Further, a genetic signature was identified in patients treated with TTFields therapy indicating an acquired immune response. Collectively, these novel preclinical and patient data further elucidate the downstream cellular processes resulting from TTFields' mechanism of action that support the potential for a therapeutic advantage when used together with immunotherapy, with limited systemic toxicity.

Based on these findings, Dr. David Tran, Chief of the Division of Neuro-Oncology, at the McKnight Brain Institute at the University of Florida, designed the phase 2 pilot 2-THE-TOP clinical study, evaluating the use of TTFields therapy together with the anti-PD-1 therapy (pembrolizumab) and chemotherapy (temozolomide) for the treatment of newly diagnosed GBM in 25 patients. In November 2021, updated data from the ongoing 2-THE-TOP study was presented at the Society for Neuro-Oncology (SNO) 2021 Annual Meeting. These preliminary data showed 19 patients with greater than 9 months of follow-up displayed a median progression-free survival (primary endpoint) of at least 11.2 months. Additionally, 193,760 peripheral blood mononuclear cells were sequenced in 12 patients before pembrolizumab was administered and detected robust post-TTFields T cell activation in 11 of 12 patients via the T1IFN trajectory with a strong correlation with the TCRαβ clonal expansion Simpson index (Spearman coefficient r=-0.8, P=0.014). This finding is in line with the JCI publication, and contributes to the building body of evidence suggesting TTFields' mechanism of action induces a downstream signaling pathway that initiates an active immune response that aids the body's ability to fight cancer cells.