Combining the strengths of cytotoxic T cells and nanomedicines for cancer immunotherapy

Cancer remains one of the most devastating diseases worldwide, with every year 14 million new cases and 8 million cancer-related deaths. Nowadays, conventional cancer therapies consist of surgery, radiotherapy, and chemotherapy. These methods, however, hold a potential risk for relapse, metastasis, and systemic toxicity. To reduce the risk of systemic toxicities, researchers have developed strategies to encapsulate chemotherapeutics in nanocarriers, aiming to improve the specific delivery of therapeutics to the tumor. Despite the success of anti-cancer nanomedicines in (pre)clinical trials, the number of commercially available therapeutics remains remarkably low. One of the main causes is their low targeting capacity and limited infiltration into the tumor after systemic injection. Therefore, this project aimed to investigate the cell-mediated delivery of nanomedicines to the tumor. For this purpose, cytotoxic T cells (CTLs) were selected as transport vehicles based on their spontaneous migration to the tumor and their potential to specifically kill tumor cells. We were the first to show the reversible coupling of lipid-based nanoparticles (NPs) to the surface of CTLs for tumor-targeted delivery of membrane-impermeable macromolecules such as small interfering RNA (siRNA). Further, preliminary in vitro and in vivo data illustrated promising results for the combination of CTLs with NPs that were loaded with immune adjuvants. Unfortunately, it has been shown in the literature that a variety of immunosuppressive mediators, especially in the tumor microenvironment, hinders the T cell anti-tumor responses. To tackle this important challenge, we developed a technique based on vapor-nanobubble photoporation for the efficient delivery of siRNA molecules to CTLs, inducing silencing of target genes. Consequently, the knockdown of important immunosuppressive pathways can give T cells more power to eradicate tumor.

Publication year:2016

Accessibility:Open