Elegant antibody nanoparticles outweigh the immunological tolerance of tumors

Immune Control Point Blocking (ICB) therapy using an antibody that fights programmed cell death ligand 1 (PD-L1) shows significant potential and is revolutionizing cancer management in the clinic. Unfortunately, only a subgroup of treated patients respond to current IIC therapies, probably because of the immunological tolerance of the tumors. Therefore, developing a practical strategy to combat this immunological tolerance and boost ICB therapies has become a priority.

To meet this challenge, scientists from the Shanghai Institute of Medical Materials (SIMM) of the Chinese Academy of Sciences have developed a nanoparticle enzymatic antibody activating the microenvironment of the tumor for a robust anti-cancer immunotherapy. This research was published online in Science Immunology.

In this study, professors Yu Haijun, Li Yaping and their colleagues developed antibody nanoparticles by integrating anti-PD-L1 (αPDL1) and indocyanine green (ICG) antibodies into a single nanoplate-form . ICG is a clinically approved fluorophore for fluorescence imaging in real surgery and a photosensitizer for photodynamic therapy (PDT). The nanoparticles of antibodies remain inert in the bloodstream and prevent αPDL1 from binding to normal tissues. Once accumulated at the tumor site through enhanced permeability and retention (EPR), the nanoparticles of antibodies activate to release αPDL1 for PD-L1-specific blockade. the tumor.

In addition, scientists have revealed that antibody nanoparticles trigger the release of tumor antigens and promote intratumoral infiltration of cytotoxic T lymphocytes (CTLs) through the ICG-based PDT effect. "This is crucial for cancer immunotherapy because CTLs have been well identified as the killer of tumor cells," explained Professor Yu, co-correspondent author of the study.

Finally, they showed that nanoparticles of antibodies not only strengthen antitumor immunity with high efficiency, but also induce long-term immune memory effects in BALB / c mice, thus leading to regression remarkable tumor.

In particular, the nanoparticle-mediated combination of ICB and PDT therapy antibodies effectively suppressed tumor growth and metastasis of the lungs and lymph nodes when using a BALB / murine model. C carrying a 4T1 tumor, which allowed the survival of> 70% of the mice. for more than 65 days, compared to complete mouse death in 42 days for the free αPDL1 group.

"We have developed a robust antibody nanoplatform designed to initiate antitumor immunity and inhibit the immune checkpoint, which could be easily adapted to other immune checkpoint inhibitors. for improved ICB therapies, generations of cancer immunotherapy, "said Professor Yu.