WCLC 2025 - Posters & ePosters-P3.03.28 Tumor Treating Fields (TTFields) Concomitantly With Anti-PD-1 and Cisplatin in a Mouse Model of Non-Small Cell Lung Cancer

P3.03.28 Tumor Treating Fields (TTFields) Concomitantly With Anti-PD-1 and Cisplatin in a Mouse Model of Non-Small Cell Lung Cancer

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This preclinical study investigated the therapeutic impact of Tumor Treating Fields (TTFields), a noninvasive anti-cancer modality using low-intensity electric fields, combined with standard immunochemotherapy—anti-PD-1 antibody, cisplatin, and pemetrexed (PCP)—in a mouse model of non-small cell lung cancer (NSCLC). C57BL/6 mice with orthotopically implanted LL/2 lung carcinoma were treated with TTFields (150 kHz), PCP, both concurrently, or controls. Treatments lasted 10 days with immunochemotherapy administered every 72 hours.<br /><br />Results demonstrated that both TTFields and PCP independently reduced tumor growth. However, combining TTFields with PCP achieved significantly greater tumor control, evident by decreased tumor volume and weight. Immunophenotyping of tumor and blood samples revealed that PCP alone and in combination with TTFields increased infiltration of total CD3+ T cells, with a prominent rise in cytotoxic CD8+ T cells within tumors. Concurrent TTFields and PCP enhanced the functional activity of tumor-infiltrating CD8+ cells, as indicated by increased production of interferon gamma (IFNγ) and granzyme B, key markers of cytotoxic immune response. Additionally, PCP treatments elevated tumor PD-L1 expression, a marker linked to inflammation and immune modulation.<br /><br />Peripheral blood analysis showed that both TTFields, PCP, and their combination raised frequencies of pre-effector CD4+ and CD8+ T cells, suggesting systemic immune activation. These findings suggest that TTFields can potentiate the efficacy of anti-PD-1 based chemotherapy by amplifying anti-tumor immune responses. This synergy provides a rationale for the ongoing clinical evaluation of TTFields combined with immunotherapy and chemotherapy in NSCLC patients, such as in the LUNAR-2 trial.<br /><br />In conclusion, the concurrent administration of TTFields with standard immunochemotherapy improved tumor suppression and enhanced cytotoxic T cell responses in this NSCLC preclinical model, indicating promising potential for integrated therapeutic strategies in lung cancer treatment.

Asset Subtitle

Anat Klein-Goldberg

Meta Tag

Speaker Anat Klein-Goldberg

Topic Tumor Biology – Translational Biology

Keywords

Tumor Treating Fields

TTFields

non-small cell lung cancer

NSCLC

immunochemotherapy

anti-PD-1 antibody

cisplatin

pemetrexed

CD8+ T cells

LUNAR-2 trial