Selective laser-tissue interaction and immunological stimulation in cancer treatment

Hyperthermia has long been considered as a potential means for cancer treatment because of the sensitivity of cancerous cells to temperature elevation. However, the thermal effect has not become the main stream of treatment modality for cancers, particularly for metastatic tumors. This is partly due to the fact that the incompleteness of the tumor cell destruction by the thermal effect and partly due to the local invasion and metastases of the remaining tumor cells. To achieve a high level photothermal selectivity in order to best use hyperthermia for cancer treatment, a combination of a near-infrared laser and a laser-absorbing dye of corresponding absorption spectrum has been used. The laser light with wavelength in the near-infrared range usually does not interact strongly with biological tissues. However, when the dye is administered to the target tissue, the laser light will be strongly absorbed by the dye molecules. The released energy from these excited molecules causes the temperature increase in the surrounding tissue. With appropriate combinations of dye doses and laser parameters, the photothermal effect can be controlled to achieve the desired outcome. The selective photothermal effect using an 805-nm diode laser and indocyanine green was studied using both chicken tissue and rat tumors. The selectivity of the combination and the temperature control were demonstrated. In the treatment of metastatic tumors, it is believed that the ultimate cure is an induced anti-tumor immunity in the host. Laser immunotherapy was proposed to achieve the induction of such an immune response. It uses the selective photothermal laser tissue interaction in combination with a special immunoadjuvant, glycated chitosan. When the immunoadjuvant is administered with the dye, followed by a non-invasive laser irradiation, it has been demonstrated that this method possesses the potential for treatment of metastatic tumors. Using an aggressive metastatic mammary tumor model, DMBA-4, laser immunotherapy resulted in eradication of treated tumors at the primary sites and regression and eradication of untreated metastases at remote sites. Furthermore, the successfully treated tumor-bearing rats showed long-term resistance to the tumors of the same origin, a clear sign of tumor imm- unity induced by the treatment. Immunological studies have shown that the sera in the successfully treated rats contain antibodies that could bind to tumor cells. The hypothesized mechanism of the induced anti-tumor immunity is a tandem effect of the photothermal effect and the immunological stimulation. The selective photothermal tissue destruction causes the tumor cell destruction and at the same time releases the tumor antigenic determinants. The immunoadjuvant is to stimulate the immune system of the host to amount a specific immune reaction against the remaining tumor cells at the primary site and its metastases. The same mechanism could also be used in other combinations, such as photodynamic therapy + adjuvant and focused ultrasound + adjuvant, to achieve the safe effect.