Phototherapy and anti-GITR antibody-based therapy synergistically reinvigorate immunogenic cell death and reject established cancers

Abstract

Phototherapy and immunogenic cell death (ICD) are powerful strategies to fight cancer. However, their therapeutic outcomes are diminished by immunosuppressive and hypoxia microenvironment. Herein, a photo-based, immunomodulating and hypoxia-alleviated nanosystem, PDA-ICG@CAT-DTA-1, is proposed to achieve the synergism between phototherapy and immunotherapy. Catalase (CAT) and anti-GITR antibody (DTA-1) are loaded to photothermal agent and photosensitizer composed PDA-ICG nanoparticles. The PDA-ICG@CAT-DTA-1 exhibits intrinsic local hyperthermia and enhanced ROS generation in tumor, and abrogates tumor immune suppression. It results in reduction of intratumoral FOXP3⁺ regulatory T cells (4.3-fold) and increase of CD4⁺ effector T cells (1.5-fold) compare with the control, and promotes damage associated molecular patterns generation to reinvigorate ICD effect. The potent antitumor of PDA-ICG@CAT-DTA-1 is proved in 4T1 bilateral tumor-bearing mice, with inhibition ratio of 95.1% for primary cancers and 68.7% for abscopal cancers. Our findings highlight great promise of the constructed versatility nanosystem to fix bottlenecks for cancer therapy.

Keywords: Anti-GITR antibody; Immunogenic cell death; Immunotherapy; Phototherapy; Tumor immune suppression.