Non-invasive laser immunotherapy (NLIT) is a treatment method for metastatic cancer which combines noninvasive laser irradiation with immunologically modified nanostructures to ablate a primary tumor and induce a systemic anti-tumor response. To further expand the development of NLIT, two different photosensitizing agents were compared: gold nanorods (GNR) with an optical absorption peak of 808 nm and indocyanine green (ICG) with an optical absorption peak of ~800 nm. Various concentrations of GNR and ICG solutions were irradiated at different power densities using an 805 nm diode laser, and the temperature of the solutions was monitored during irradiation using a thermal camera. For comparison, dye balls made up of a 1:1 volume ratio of gel solution to GNR or ICG solution were placed in phantom gels and were then irradiated using the 805 nm diode laser to imitate the effect of laser irradiation on in vivo tumors. Non-invasive laser irradiation of GNR solution for 2 minutes resulted in a maximum increase in temperature by 31.8 °C. Additionally, similar irradiation of GNR solution dye ball within phantom gel for 10 minutes resulted in a maximum temperature increase of 8.2 °C. Comparatively, non-invasive laser irradiation of ICG solution for 2 minutes resulted in a maximum increase in temperature by 28.0 °C. Similar irradiation of ICG solution dye ball within phantom gel for 10 minutes yielded a maximum temperature increase of only 3.4 °C. Qualitatively, these studies showed that GNR solutions are more effective photosensitizing agents than ICG solution.
Laser immunotherapy (LIT) uses laser irradiation and immunological stimulation to target all types of metastases and creates a long-term tumor resistance. Glycated chitosan (GC) is the immunological stimulant used in LIT. Interestingly, GC can act as a surfactant for single-walled carbon nanotubes (SWNTs) to immunologically modify SWNTs. SWNT-GC retains the optical properties of SWNTs and the immunological functions of GC to help increase the selectivity of the laser and create a more optimal immune response. One essential aspect of understanding this immune response is knowing how laser irradiation affects cancer cells’ ability to metastasize. In this experiment, a cell migration assay was performed. A 2mm circular elastomer plugs were placed at the bottom of multi-well dishes. Pre-cancerous keratinocytes, different tumor cells, and fibroblasts were then plated separately in treated wells. Once the cells reached 100% confluence, they were irradiated by either a 980nm or 805nm wavelength laser. The goal was to determine the effects of laser irradiation and immunological stimulation on cancer cell migration in vitro, paying the way to understand the mechanism of LIT in treating metastatic tumors in cancer patients.
Clinical trials of late-stage breast cancer patients and late-stage melanoma patients treated by laser immunotherapy (LIT) have shown promising results. In a 2010 study of Li et al, eleven late-stage melanoma patients received LIT in one or multiple 6-week treatment cycles applied to a 200-cm2 treatment site, which usually contained multiple cutaneous metastases. Long-term, positive response was observed in six patients. All lesions in the treatment area of the patients responded to LIT, eight of which achieved complete local response (CLR). CLR was observed in the non-treatment site (regional) lesions in four patients. Five patients were still alive at the time of last follow-up. The probability of 12-month overall survival was 70%.2 In 2011, Li et al, treated ten late stage breast cancer patients with LIT.1 In 8 patients available for evaluation, the objective response rate was 62.5% and the clinical beneficial response rate was 75%.1 This review demonstrates that LIT is safe and well tolerated, so it can be easily applied on an outpatient basis and can be combined with other pharmaceutical modalities to improve the therapeutic response of metastatic cancers.
Laser immunotherapy (LIT) is an innovative cancer modality that uses laser irradiation and immunological stimulation to treat late-stage, metastatic cancers. LIT can be performed through either interstitial or non-invasive laser irradiation. Although LIT is still in development, recent clinical trials have shown that it can be used to successfully treat patients with late-stage breast cancer and melanoma. The development of LIT has been focused on creating an optimal immune response created by irradiating the tumor. One important factor that could enhance the immune response is the duration of laser irradiation. Irradiating the tumor for a shorter or longer amount of time could weaken the immune response created by LIT. Another factor that could weaken this immune response is the proliferation of regulatory T cells (TRegs) in response to the laser irradiation. However, low dose cyclophosphamide (CY) can help suppress the proliferation of TRegs and help create a more optimal immune response. An additional factor that could weaken the effectiveness of LIT is the selectivity of the laser. If LIT is performed non-invasively, then deeply embedded tumors and highly pigmented skin could cause an uneven temperature distribution inside the tumor. To solve this problem, an immunologically modified carbon nanotube system was created by using an immunoadjuvant known as glycated chitosan (GC) as a surfactant for single-walled carbon nanotubes (SWNTs) to immunologically modify SWNTs. SWNT-GC retains the optical properties of SWNTs and the immunological functions of GC to help increase the selectivity of the laser and create a more optimal immune response. In this preliminary study, tumor-bearing rats were treated with LIT either interstitially by an 805-nm laser with GC and low-dose CY, or non-invasively by a 980-nm laser with SWNT-GC. The goal was to observe the effects of CY on the immune response induced by LIT and to also determine the effect of irradiation duration for interstitial and noninvasive LIT.
Laser immunotherapy (LIT) is being developed as a treatment modality for metastatic cancer which can destroy primary tumors and induce effective systemic anti-tumor responses by using a targeted treatment approach in conjunction with the use of a novel immunoadjuvant, glycated chitosan (GC). In this study, Non-invasive Laser Immunotherapy (NLIT) was used as the primary treatment mode. We incorporated single-walled carbon nanotubes (SWNTs) into the treatment regimen to boost the tumor-killing effect of LIT. SWNTs and GC were conjugated to create a completely novel, immunologically modified carbon nanotube (SWNT-GC). To determine the efficacy of different laser irradiation durations, 5 minutes or 10 minutes, a series of experiments were performed. Rats were inoculated with DMBA-4 cancer cells, a highly aggressive metastatic cancer cell line. Half of the treatment group of rats receiving laser irradiation for 10 minutes survived without primary or metastatic tumors. The treatment group of rats receiving laser irradiation for 5 minutes had no survivors. Thus, Laser+SWNT-GC treatment with 10 minutes of laser irradiation proved to be effective at reducing tumor size and inducing long-term anti-tumor immunity.
T-cell stimulators such as anti-CTLA-4 antibodies enhance immunologic responses to chemotherapy-resistant solid tumors, such as melanoma, advanced breast cancer, ovarian cancer and pancreatic cancer. The efficacy of these new immunotherapy agents can in theory be enhanced substantially by therapies that stimulate new immunologic (T-cell) responses against the tumor. Laser immunotherapy (LIT) with imiquimod and InCVAX are techniques that produce useful responses in patients with advanced melanoma, the prototypical chemotherapy resistant solid tumor. The mechanism of action of these therapies is thought to be immunological, including the development of new T-cell responses. We have therefore been combining LIT using imiquimod and InCVAX treatment with the new T-cell stimulators (ipilimumab) in cases of stage IV melanoma. While still anecdotal, the use of novel combinations of immunologic therapies should provide much improved responses for chemotherapy-resistant solid tumors (such as melanoma) than was previously possible. Newer T-cell stimulating drugs such as the anti-PD-1 antibodies and anti-PD-L1 antibodies will make this general approach to treating chemoresistant advanced tumors even more effective in the future.
Laser immunotherapy (LIT) is an innovative cancer modality that uses laser irradiation and immunological stimulation to treat late-stage, metastatic cancers. The current mode of operation in LIT is through interstitial laser irradiation. Although LIT is still in development, recent clinical trials have shown that it can be used to successfully treat patients with late-stage breast cancer and melanoma. Cyclophosphamide is a chemotherapy drug that suppresses regulatory T cells when used in low doses. In this study tumor-bearing rats were treated with LIT using an 805-nm laser with a power of 2.0 W and low-dose cyclophosphamide. Glycated chitosan was used as an immunological stimulant. The goal was to observe the effects of different doses of cyclophosphamide in addition to LIT on the survival of the tumor-bearing rats.
Laser immunotherapy (LIT) uses laser irradiation and immunological stimulation to treat metastatic cancers.
The current mode of operation of LIT is through dye-enhanced non-invasive irradiation. Although this
treatment has given promising results, there are still a number of challenges with this method, such as
limited light penetration for deep tumors and strong light absorption by highly pigmented skins. Interstitial
laser immunotherapy (ILIT), using a cylindrical diffuser, is designed to overcome these limitations. In this
study, rat tumors were treated by ILIT with an 805 nm laser and varying doses of glycated chitosan, an
immunological stimulant. The goal was to observe the effects of differing doses of the stimulant on the
survival of the tumor-bearing rats. The results suggested that the optimal dose of glycated chitosan is in the
range of 0.1 to 0.3 ml per rat tumor.