Enhancement of Laser Cancer Treatment by a Chitosan-derived Immunoadjuvant¶

Abstract

A chitosan derivative, glycated chitosan (GC), has been used as an immunostimulant for cancer treatment in laser immunotherapy. The function of GC is to enhance the host immune response after direct cancer cell destruction by a selective laser photothermal interaction. To further test its effects, laser immunotherapy was extended to include several different adjuvants for immunological stimulation and to include photodynamic therapy (PDT) as a different tumor-destruction mechanism. Complete Freund (CF) adjuvant, incomplete Freund (IF) adjuvant and Corynebacterium parvum (CP) were selected for treatment of metastatic mammary tumors in rats, in combination with a selective photothermal interaction. The solution of the immunoadjuvants admixed with indocyanine green (ICG), a light-absorbing dye, was injected directly into the tumors, followed by noninvasive irradiation of an 805 nm laser. Combined with PDT, in the treatment of tumors in mice, GC was administered peritumorally immediately after laser irradiation. The survivals of treated animals were compared with untreated control animals. In the treatment of rat tumors, CF, IF and CP raised the cure rates from 0% to 18%, 7% and 9%, respectively. In comparison, GC resulted in a 29% long-term survival. In the treatment of EMT6 mammary sarcoma in mice, GC of 0.5% and 1.5% concentrations increased the cure rates of Photofrin-based PDT treatment from 38% to 63% and 75%, respectively. In the treatment of Line 1 lung adenocarcinoma in mice, a 1.67% GC solution enabled a noncurative meso-substituted tetra(meta-hydroxy-phenyl)chlorin-based PDT to cure 37% of the tumor-bearing mice. The experimental results of this study confirmed our previous studies, showing that immunoadjuvants played an active role in laser-related cancer treatment and that GC significantly enhanced the efficacy of laser cancer treatment.

Liposomal photosensitizers: potential platforms for anticancer photodynamic therapy

“…This finding suggests that formulations containing not only photosensitizer but also strong immune adjuvants could improve the long-term effectiveness of PDT and also relating the use of immunoadjuvants with an improvement in the antineoplastic PDT (47,54).…”

“…However, despite the important immune adjuvanticity exerted by the cellular debris, some studies have related the local application of exogenous immune adjuvants to a significant improvement of PDT-induced tumor immunization (54). This finding suggests that formulations containing not only photosensitizer but also strong immune adjuvants could improve the long-term effectiveness of PDT and also relating the use of immunoadjuvants with an improvement in the antineoplastic PDT (47,54).…”

Photodynamic therapy plus low-dose cyclophosphamide generates antitumor immunity in a mouse model

“…However, mounting evidence suggests that, as opposed to many common cancer therapies that are largely immunosuppressive, PDT can stimulate the immune system (16). In this respect PDT is similar to adjuvant-enhanced laser immunotherapy that has also been shown to be capable of destroying local tumors, while at the same time sensitizing the immune system to destroy distant metastases (48)(49)(50)(51). The fact that we observed only long-term cures with the low-dose CY combination treatment suggests that in this tumor model (and perhaps in many others) there is some host factor that is fighting against the immune stimulating effect of PDT.…”

Multifunctional Chitosan Nanoparticles for Tumor Imaging and Therapy

“…In the last decade, many promising results have been obtained for lung cancer, head and neck cancer, skin cancer, locoregional breast cancer recurrences, and prostate cancer [71,72]. PDT is also an attractive clinical modality for several other therapeutic applications like inflammations [73].…”