Mechanism of laser immunotherapy - Role of immunoadjuvant and selective photothermal laser-tissue interaction

摘要

Immunotherapy has been used for cancer treatment in the past century. Although different approaches have been attempted, the basic strategy has been targeting specific tumor antigens to induce host immune responses. Laser immunotherapy is a novel approach in treating metastatic tumors. The combination of two major interactions in laser immunotherapy - selective photothermal and photoimmunological interactions - is designed to induce a tumor-specific host immune response. The hypothetical mechanism is as follows. The intratumor injection of laser-absorbing dye and the non-invasive irradiation of a near-infrared laser produce an acute, selective thermal tumor killing, and at the same time, release tumor antigens. The in situ immunoadjuvant then combines with the liberated tumor antigens to stimulate and direct the host immune system to fight against remaining tumor cells both locally and in remote metastatic sites. In effect, an in situ vaccination against the tumor was achieved. Such an immune response eventually leads to a systemic, long term tumor resistance. Our pre-clinical animal studies have demonstrated such a long-term immunity. Specifically, a novel immunoadjuvant, glycated chitosan (GC), was used in laser immunotherapy. Because the use of immunoadjuvant is crucial in cancer immunotherapy, the role of GC was investigated. Different permutations using the three components of laser immunotherapy were used in treating metastatic mammary tumors in rats. Our results indicated that only when GC was used the treatment of metastatic mamary rat tumors could be successful and the laser-dye-adjuvant combination provided the most effective treatment outcomes. the selective photothermal interaction using laser and indocyanine green was also studied in terms of tissue temperature increases. A gel phantom was used to simulate tissue with a deeply embedded, dyeenhanced target tissue. Our results indicated that with laser-ICG combination, the photothermal interaction can be highly selective and optimal treatment could be obtained by choosing appropriate operating parameters.