Systemic Multifrequency Electromagnetic Pulses Is an Efficient Therapy for Established Tumors in Immunocompetent Mice

We previously established that Multifrequency Electromagnetic Pulse (MEMP) treatment selectively eradicates tumorigenic cells in vitro. While this treatment proved safe in mice and prevented tumor formation by pre-treated cells, its efficacy against established tumors remained unknown. Here we evaluate the therapeutic effect of two different systemic MEMP treatment regimens (30 Hz, >2 T) on syngeneic MC38 colon adenocarcinoma es-tablished subcutaneously in C57BL/6 mice. The impact of MEMP on anti-tumor immune infiltration (CD4, CD8, CD68) responses, as well as oxidative stress (HO-1, MDA), and DNA damage (γH2AX), cell biology markers, were analyzed by immunohistochemistry. The MEMP regimes significantly reduced the growth of the xenografted tumors leading to an apparent regression in a small subset of animals, and extended survival without af-fecting animal welfare. Of note, mice that achieved complete tumor regression mounted a protective immune response, demonstrating robust resistance to a subsequent tumor re-challenge, indicative of immunological memory. Importantly, the quantitative penetra-tion of immune effectors CD68+ cells into tumors suggests the involvement of a strong, macrophage-mediated anti-tumor response, although the ultimate mechanisms driving the MEMP effects in vivo deserve further research. These findings place MEMP as a prom-ising anti-cancer treatment and a strong candidate procedure for combination with other systemic immunotherapies.