Combining targeted photothermal therapy with a locally administered novel immunostimulant for treatment of metastatic cancers: from benchtop to bedside

The biggest challenge in cancer treatment is metastasis, due to the failure of the host immune system to detect and destroy cancer cells, particularly metastatic tumor cells. In fact, about 90% of cancer deaths are caused by metastasis. Unfortunately, we have limited options for treating metastatic cancers. Given the immunological root cause of cancer, the ideal solution is immunotherapy to activate, enhance, and direct the host immune system to systemically eradicate cancer and prevent recurrence. However, current immunotherapies have limitations. Even advanced immunotherapies, such as immune checkpoint blockade, have a low patient response rate, around 10 to 30%. To overcome these limitations, particularly the challenges posed by metastatic tumors—which are often not detectable or treatable, we developed localized ablative immunotherapy (LAIT). LAIT combines targeted photothermal therapy with a locally administered novel immunostimulant to induce systemic immune responses aimed at treating metastatic tumors. In this talk, I will first review the development of this unique modality, specifically the treatment procedure and mechanism of action. I will discuss LAIT-induced immune responses at the transcriptomic level using single-cell RNA sequencing. Then, I will present our clinical results using LAIT for the treatment of patients with melanoma, breast cancer, and other late-stage cancers