Abstract
Thermal ablation is a standard therapy for patients with hepatocellular carcinoma (HCC). Contemporary ablation devices are imperfect, as they lack tumor specificity. An ideal ablation modality would generate thermal energy only within tumoral tissue. Furthermore, as hyperthermia is known to influence tumor immunity, such a tumor-specific ablation modality may have the ability to favorably modulate the tumor immune landscape. Here we show a clinically relevant thermal ablation modality that generates tumor-specific hyperthermia, termed molecularly targeted photothermal ablation (MTPA), that is based upon the excellent localization of indocyanine green to HCC. In a syngeneic rat model, we demonstrate the tumor-specific hyperthermia generated by MTPA. We also show through spatial and transcriptomic profiling techniques that MTPA favorably modulates the intratumoral myeloid population towards tumor immunogenicity and diminishes the systemic release of oncogenic cytokines relative to conventional ablation modalities.
Highlights
Thermal ablation is a standard therapy for patients with hepatocellular carcinoma (HCC)
Termed molecularly targeted photothermal ablation (MTPA), this technology builds upon prior work in which we have demonstrated that the clinically available near-infrared (NIR) fluorescent drug indocyanine green (ICG) to HCC with exceptional target-to-background ratios (TBRs)[21,22]
The fact that MTPA relies on clinically approved drugs and devices reinforces its clinical translatability and underlines the technology’s potential for clinical impact
Summary
Thermal ablation is a standard therapy for patients with hepatocellular carcinoma (HCC). We show a clinically relevant thermal ablation modality that generates tumor-specific hyperthermia, termed molecularly targeted photothermal ablation (MTPA), that is based upon the excellent localization of indocyanine green to HCC. For patients with small HCC lesions, though, local tumor control with thermal ablation such as radiofrequency ablation (RFA) is highly effective and is the standard of care[4]. Contemporary ablation modalities, including RFA, are imperfect for several reasons These procedures are typically performed under imaging guidance using computed tomography (CT) imaging, target lesions may be poorly visualized; the ablation devices have no methods for confirming appropriate positioning within the target lesion[5]. An ideal ablation modality would have the ability to provide the interventionalist with real-time feedback regarding the accuracy of the ablation needle’s positioning within the tumor It would exhibit tumor specificity, generating thermal energy only within tumoral tissue
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