TY - JOUR T1 - Anti-tumor efficacy of combination integrin αvβ6-targeted photodynamic therapy and immune checkpoint inhibition JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 85 LP - 85 VL - 57 IS - supplement 2 AU - Liquan Gao AU - Chenran Zhang AU - Duo Gao AU - Hao Liu AU - Fan Wang AU - Zhaofei Liu Y1 - 2016/05/01 UR - http://jnm.snmjournals.org/content/57/supplement_2/85.abstract N2 - 85Objectives Educating the host immune system to recognize and systemically eliminate residual tumor lesions and micrometastases is a promising strategy for cancer therapy. In this study, we investigated whether integrin αvβ6-targeted photodynamic therapy (PDT) of tumors using a phthalocyanine dye-labeled probe (termed DSAB-HK) could trigger the host immune response, and whether PDT in combination with immune checkpoint inhibition could be used for the effective therapy of primary tumor and metastases.Methods DSAB-HK was prepared by mixing IRDye700-labeled streptavidin with biotin-conjugated HK peptide (integrin αvβ6-specific). Near-infrared fluorescence (NIRF) imaging was performed to evaluate the in vivo tumor targeting of DSAB-HK. The antitumor efficacy of DSAB-HK in combination of anti-PD-1 immune checkpoint inhibition was determined in vivo.Results By NIRF imaging, DSAB-HK was demonstrated to specifically target either subcutaneous tumors in a 4T1 mouse breast cancer model or lung metastatic firefly luciferase stably transfected 4T1 (4T1-fLuc) tumors. Upon light irradiation, PDT by DSAB-HK significantly inhibited the growth of subcutaneous 4T1 tumors, and in addition promoted the maturation of dendritic cells and their production of cytokines, which subsequently stimulated the tumor recruitment of CD8+ cytotoxic T lymphocytes. Furthermore, DSAB-HK PDT of the first tumor followed by PD-1 blockage markedly suppressed the growth of a second subcutaneous tumor, and also slowed the growth of 4T1-fLuc lung metastasis as demonstrated by serial bioluminescence imaging.Conclusions Our results demonstrated the synergistic effect of tumor-targeted PDT and immune checkpoint inhibition for improving antitumor immunity and suppressing tumor metastases. $$graphic_E8F9E6E7-6E5C-4F3F-BF00-A437D5113E52$$ ER -