Anti-tumor immunological response induced by local intervention is ideal for treatment of metastatic tumors. Laser immunotherapy was developed to synergize photothermal interaction with immunological stimulation for cancer treatment. Using an infrared laser, indocyanine green (ICG, as a light absorbing agent), and glycated chitosan (GC, as an immunostimulant), laser immunotherapy has resulted in tumor suppression and anti-tumor responses in pre-clinical as well as clinical studies. To further understand the mechanism of laser immunotherapy, the effects of laser and GC treatment without specific enhancement of laser absorption were studied. Passive adoptive immunity transfer was performed using splenocytes as immune cells. Spleen cells harvested from tumor-bearing mice treated by laser + GC provided 60% immunity in naive recipients. Furthermore, cytotoxicity and TNF-α secretion by splenocytes from treated mice also indicated that laser + G induced immunity was tumor-specific. The high level of infiltrating T cells in tumors after laser + GC treatment further confirmed a specific anti-tumor immune response. Therefore, laser + GC could prove to be a promising selective local treatment modality that induces a systemic anti-tumor response, with appropriate laser parameters and GC doses.

The ideal treatment modality for metastatic cancer would be a local treatment that can destroy primary tumors while inducing an e®ective systemic anti-tumor response. To this end, we developed laser immunotherapy, combining photothermal laser application with an immunoadjuvant for the treatment of metastatic cancer. Additionally, to enhance the selective photothermal e®ect, we integrated light-absorbing nanomaterials into this innovative treatment. Speci¯cally, we developed an immunologically modi¯ed carbon nanotube combining single-walled carbon nanotubes (SWNTs) with the immunoadjuvant glycated chitosan (GC). To determine the effectiveness of laser irradiation, a series of experiments were performed using two di®erent irradiation durations -5 and 10 min. Rats were inoculated with DMBA-4 cancer cells, a metastatic cancer cell line. The treatment group of rats receiving laser irradiation for 10 min had a 50% longterm survival rate without residual primary or metastatic tumors. The treatment group of rats receiving laser irradiation for 5 min had no long-term survivors; all rats died with multiple metastases at several distant sites. Therefore, LaserþSWNT-GC treatment with 10 min of laser ¶ Corresponding author. This is an Open Access article published by World Scienti¯c Publishing Company. It is distributed under the terms of the Creative Commons Attribution 3.0 (CC-BY) License. Further distribution of this work is permitted, provided the original work is properly cited. Vol. 8, No. 4 (2015) 1550036 (8 pages irradiation proved to be e®ective at reducing tumor size and inducing long-term anti-tumor immunity. Journal of Innovative Optical Health Sciences

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While successes of different cancer therapies have been achieved in various degrees a systemic immune response is needed to effectively treat late-stage, metastatic cancers, and to establish long-term tumor resistance in the patients. A novel method for combating metastatic cancers has been developed using immunologically modified carbon nanotubes in conjunction with phototherapy. Glycated chitosan (GC) is a potent immunological adjuvant capable of increasing host immune responses, including antigen presentation by activation of dendritic cells (DCs) and causing T cell proliferation. GC is also an effective surfactant for nanomaterials. By combining single-walled carbon nanotubes (SWNTs) and GC, immunologically modified carbon nanotubes (SWNT-GC) were constructed. The SWNT-GC suspension retains the enhanced light absorption properties in the near infrared (NIR) region and the ability to enter cells, which are characteristic of SWNTs. The SWNT-GC also retains the immunological properties of GC. Cellular SWNT-GC treatments increased macrophage activity, DC activation and T cell proliferation. When cellular SWNT-GC was irradiated with a laser of an appropriate wavelength, these immune activities could be enhanced. The combination of laser irradiation and SWNT-GC induced cellular toxicity in targeted tumor cells, leading to a systemic antitumor response.Immunologically modified carbon nanotubes in conjunction with phototherapy is a novel and promising method to produce a systemic immune response for the treatment of metastatic cancers.