Co-delivery of nucleoside-modified mRNA and TLR agonists for cancer immunotherapy: Restoring the immunogenicity of immunosilent mRNA.

This study reports on the design of mRNA and adjuvant-loaded lipid nanoparticles for therapeutic cancer vaccination. The use of nucleoside-modified mRNA has previously been shown to improve the translational capacity and safety of mRNA-therapeutics, as it prevents the induction of type I interferons (IFNs). However, type I IFNs were identified as the key molecules that trigger the activation of antigen presenting cells, and as such drive T cell immunity.

Comparing photoporation and nucleofection for delivery of small interfering RNA to cytotoxic T cells.

The success of cancer immunotherapy through the adoptive transfer of cytotoxic T lymphocytes (CTLs) is highly dependent on the potency of the elicited anti-tumor responses generated by the transferred cells, which can be hindered by a variety of upregulated immunosuppressive pathways. Downregulation of these pathways in the T cells via RNA interference (RNAi) could significantly boost their capacity to infiltrate tumors, proliferate, persist, and eradicate tumor cells, thus leading to a durable anti-tumor response. Unfortunately, it is well known that primary T cells are hard-to-transfect and conventional non-viral transfection agents are generally ineffective.

Hitchhiking nanoparticles: Reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes.

Following intravenous injection of anti-cancer nanomedicines, many barriers need to be overcome en route to the tumor. Cell-mediated delivery of nanoparticles (NPs) is promising in terms of overcoming several of these barriers based on the tumoritropic migratory properties of particular cell types. This guided transport aims to enhance the NP accumulation in the tumor and moreover enhance the infiltration of regions that are typically inaccessible for free NPs.

A personalized view on cancer immunotherapy.

Recent progress in cancer immunotherapy has resulted in complete responses in patients refractory to current standard cancer therapies. However, due to tumor heterogeneity and inter-individual variations in anti-tumor immunity, only subsets of patients experience clinical benefit. This review highlights the implementation of a personalized approach to enhance treatment efficacy and reduce side effects, including the identification of tumor-specific antigens for cancer vaccination and adoptive T cell therapies.