Abstract
Immunochemotherapy combines a chemotherapeutic agent with an immune-modulating agent and represents an attractive approach to improve cancer therapy. However, the success of immunochemotherapy is hampered by the lack of a strategy to effectively co-deliver the two therapeutics to the tumours. Here we report the development of a dual-functional, immunostimulatory nanomicellar carrier that is based on a prodrug conjugate of PEG with NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor currently used for reversing tumour immune suppression. An Fmoc group, an effective drug-interactive motif, is also introduced into the carrier to improve the drug loading capacity and formulation stability. We show that PEG2k-Fmoc-NLG alone is effective in enhancing T-cell immune responses and exhibits significant antitumour activity in vivo. More importantly, systemic delivery of paclitaxel (PTX) using the PEG2k-Fmoc-NLG nanocarrier leads to a significantly improved antitumour response in both breast cancer and melanoma mouse models.
Highlights
Immunochemotherapy combines a chemotherapeutic agent with an immune-modulating agent and represents an attractive approach to improve cancer therapy
We have recently shown that incorporation of an Fmoc motif into a micellar system can improve the drug loading capacity and formulation stability and broaden its utility in formulating various therapeutic agents of diverse structures[23,24]
Similar results were obtained when the Trp and Kyn concentrations were measured by high-performance liquid chromatography–mass spectrometry (HPLC–MS) (Supplementary Fig. 7)
Summary
Immunochemotherapy combines a chemotherapeutic agent with an immune-modulating agent and represents an attractive approach to improve cancer therapy. Systemic delivery of paclitaxel (PTX) using the PEG2k-Fmoc-NLG nanocarrier leads to a significantly improved antitumour response in both breast cancer and melanoma mouse models. The effectiveness of chemotherapy-elicited immune response as well as other types of immunotherapies is limited by various negative feedback mechanisms that are upregulated during tumour development and/or cancer treatment[9,10]. Co-delivery of IDO inhibitors and chemotherapeutic agents to tumours remains a challenge due to their different physical and pharmacokinetic profiles To resolve these challenges, we develop a novel micellar nanocarrier that is based on PEG-derivatized NLG919 prodrug. Systemic delivery of PTX using the PEG2k-Fmoc-NLG nanocarrier leads to a significantly improved antitumour effect in both breast cancer and melanoma mouse models
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
