Efficacy of ZnPcS₂P₂ photodynamic therapy solely or with tumor vaccines on mouse tumor models

Summary 

Background and objectives

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and B7.1 transduced tumor vaccine cells could induce efficient anti-tumor immune response. It is interesting to study whether they could be an adjuvant to photodynamic therapy (PDT). Recent in vitro study proved that novel photosensitizer ZnPcS₂P₂ has capability of effective photodynamic killing of leukemic cells. In this preliminary study, we evaluated the photodynamic efficacy of ZnPcS₂P₂ on two tumor models and the improving anti-tumor efficacy of PDT in combination with GM-CSF gene-transduced vaccine and B7.1 gene-transduced vaccine.

Methods

Nude mice bearing human leukemia xenograft and C57BL/6 mice bearing EL-4 thymic lymphoma were used to evaluate photodynamic efficacy of ZnPcS₂P₂. The EL-4 thymic lymphoma was used to test the improving anti-tumor efficacy of ZnPcS₂P₂-PDT in combination with GM-CSF gene-transduced vaccine and B7.1 gene-transduced vaccine. Each vaccine was administered near the tumor bed three times: 2 days before PDT, 0 and 2 days after PDT.

Results

ZnPcS₂P₂-PDT could significantly reduce tumor growth and prolong the survival time in both tumor models. Improving anti-tumor efficacy of ZnPcS₂P₂-PDT was demonstrated when utilizing GM-CSF-transduced vaccine and B7.1-transduced vaccine prior to and after ZnPcS₂P₂-PDT in lymphoma-bearing mice. Twenty-five percent of lymphoma-bearing mice were completely cured with a combination of PDT and vaccine cells.

Conclusions

ZnPcS₂P₂-PDT may be a beneficial treatment for hemotopoietic malignance. GM-CSF-transduced vaccine and B7.1-transduced vaccine could strengthen ZnPcS₂P₂-PDT-elicited anti-lymphoma potency.

Keywords: Photodynamic therapy, Zinc phthalocyanine, Immune gene therapy, Leukemia, Lymphoma