Elegant antibody nanoparticles override immunological tolerance of tumours

15 Jul 2019

Immune checkpoint blockade (ICB) therapy using the antibody that combats the programmed cell death ligand 1 (PD-L1) shows great potential and is causing a revolution in clinical cancer management.

Unfortunately, only a subset of treated patients responds to current ICB therapies, likely due to the immunological tolerance of tumours.

Therefore, developing a practical strategy to combat this immunological tolerance and amplify ICB therapies has become a priority.

To meet this challenge, scientists from the Shanghai Institute of Materia Medica (SIMM) of the Chinese Academy of Sciences have developed a tumour enzymatic microenvironment-activatable antibody nanoparticle for robust cancer immunotherapy.

This research was published in  the journal Science Immunology.

In this study, Prof Yu Haijun, Prof Li Yaping and their colleagues engineered the antibody nanoparticles by integrating anti-PD-L1 antibody (αPDL1) and indocyanine green (ICG) into one single nanoplatform.

ICG is a clinically approved fluorophore for fluorescence imaging in live surgery and photosensitiser for photodynamic therapy (PDT).

The antibody nanoparticles remain inert in blood circulation and protect αPDL1 from binding with normal tissues.

Once accumulated at the tumour site through the enhanced permeability and retention (EPR) effect, the antibody nanoparticles become activated to release αPDL1 for tumour-specific PD-L1 blockading.

Moreover, the scientists revealed that the antibody nanoparticles triggered the release of tumour antigens and promoted intratumoural infiltration of cytotoxic T lymphocytes (CTLs) through the ICG-based PDT effect.

"This is crucial for cancer immunotherapy since CTLs have been well-identified as the killer of tumour cells," explained Prof Yu, the co-corresponding author of the study.

Finally, they showed that the antibody nanoparticles not only boost anti-tumour immunity with great efficiency, but also elicit long-term immune memory effects in BALB/c mice, thus leading to remarkable tumour regression.

In particular, the antibody nanoparticle-mediated combination of ICB and PDT therapy effectively suppressed tumour growth and metastasis to the lung and lymph nodes when using a 4T1 tumour-bearing BALB/C mouse model, which resulted in survival for >70 percent of the mice for more than 65 days, compared to complete mouse death in 42 days for the free αPDL1 group.

"We provided a robust antibody nanoplatform for priming the anti-tumour immunity and inhibiting the immune checkpoint, which could be readily adapted to other immune checkpoint inhibitors for enhanced ICB therapies. Given the simplicity of the nanostructures, our study has the potential of being translated into future generations of cancer immunotherapy," Prof Yu concluded.

Source: Chinese Academy of Sciences Headquarters

Image credit: Wang Dangge