ANTI-TUMOR RESPONSES INDUCED BY LASER IRRADIATION AND IMMUNOLOGICAL STIMULATION USING A MOUSE MAMMARY TUMOR MODEL

Feifan Zhou,Sheng Song,Wei R Chen,Eric W Howard,Xiaosong Li,Roman F Wolf,Joseph T Acquaviva

doi:10.1142/s1793545813500399

Abstract

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.

Highlights

Laser immunotherapy (LIT) was developed to combine photothermal interaction with immunological stimulation to treat metastatic tumors.[1,2] Its selective photothermal e®ect serves as therst line of assault on the tumor, using a combination of a near-infrared laser irradiation and a light-absorbing dye.[3]
The mice treated by laser or laser þ glycated chitosan (GC) had an average tumor burden noticeably smaller than that of the control mice [see Fig. 1(a)]
Laser or laser þ GC treatment induced about 50% cell death rate [see Fig. 1(b)]

Summary

Introduction

Laser immunotherapy (LIT) was developed to combine photothermal interaction with immunological stimulation to treat metastatic tumors.[1,2] Its selective photothermal e®ect serves as therst line of assault on the tumor, using a combination of a near-infrared laser irradiation and a light-absorbing dye.[3]. A new compound, glycated chitosan (GC), derived from chitosan by attaching galactose molecules to the chitosan molecules, was developed as a novel immunostimulant.[1,4] GC, as a water soluble compound, is more suitable for in vitro and in vivo biomedical applications.[5,6] LIT using dye-enhanced thermal interaction and GC has been proven to be highly e®ective in the treatment of metastatic tumors in animal studies and pre-clinical studies.[7,8,9,10,11]

Methods

Results

Conclusion