PhD Scientific Days 2026

Poster Session 3.J - Theoretical and Translational Medicine

Enhancing the Efficacy of Immune Checkpoint Blockade by Modulated Electro-hyperthermia in Colorectal Cancer Model

Name of the presenter

Elsalahaty, Mohamed Ismail Abdrabelnaby

Institute/workplace of the presenter

Institute of Clinical Pathophysiology

Authors

Mohamed I. Elsalahaty¹, Eslam Abdalalem¹, Hakim Bahlok Jebur¹, Cedrik F. W. Kintscher¹, Mingming He¹, Dániel Bócsi¹, Qusay O. Abdalla¹, Yibo Gu¹, Ebsa Tofik Ahmed¹, Zoltán Koós¹, Csaba András Schvarcz¹, Péter Hamar¹
1: Institute of Clinical Pathophysiology - Semmelweis University - 1094, Tűzoltó utca, 37-49, Budapest, Hungary

Text of the abstract

Introduction: Immune checkpoint blockade (ICB) acts conceptually as a pro-drug, with T cells as effectors. In metastatic colorectal cancer (mCRC), ICB benefits mainly the ~15% microsatellite high (MSI-H) patients’ cohort, commonly modeled by MC38 in mice; however, primary and acquired resistance still exist. Modulated electro-hyperthermia (mEHT; 13.56 MHz) selectively increases intratumoral temperature (temp), inducing tumor debulking and immunogenic cell death (ICD) via thermal and electromagnetic effects. . mEHT has a safe therapeutic profile and shown efficacy in preclinical cancer settings and demonstrated abscopal effects in a phase III trial, suggesting systemic immune activation.
Materials and Methods: Subcutaneous MC38 tumors were established in female C57BL/6 mice and randomized on day 8 into Vehicle+Sham, mEHT inducing intratumoral temp of 39.5 °C or 42.5 ~°C ± anti-PD-L 1groups. Skin temp was monitored and power adjusted to approximately 2.5 °C below the intended intratumoral temp, based on our prior work. mEHT was applied on days 9, 11, 13, and 14, and anti–PD-L1 (atezolizumab, 300 µg i.p.) on days 8, 10, 12, 14, 16, and 18. Tumor growth and body weight were monitored every other day by ultrasound and scale, and mice were sacrificed on day 22 for immunohistochemical and molecular analyses.
Results: Only mEHT inducing intratumoral temp ~ 42.5 °C excreted therapeutic effects and, when combined with ICB significantly regressed tumor growth, including near complete response in some cases (P= 0.0198, vs Vehicle + Sham; P = 0.0026 vs mEHT 39.5 °C ; P = 0.0133 vs mEHT 39.5 °C + ICB), however mEHT at lower power inducing ≈39.5°C intratumoral temp, either alone or with ICB, was not sufficient, indicating that higher power is required for anti-tumor efficacy. No significant changes in body weight were observed among groups (e.g., ICB + mEHT ~42.5 5 °C vs Vehicle + Sham, P=0.7128), supporting the safety of the combination.
Conclusion: mEHT combined with ICB significantly suppressed tumor growth with no detectable toxicity. These results support further mechanistic studies and evaluation of this strategy across additional cancer models.