Editors' ChoiceCancer Therapy

Conjugation does not conquer all in cancer nanotherapy

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Science Translational Medicine  12 Jul 2017:
Vol. 9, Issue 398, eaan8204
DOI: 10.1126/scitranslmed.aan8204


Vaccination with potato virus X nanoparticles enhances the efficacy of traditional doxorubicin anticancer therapy against a mouse melanoma tumor model.

Due to its ability to evade immune responses, become resistant against cytotoxic insults, rapidly divide, and spread throughout the body, cancer is one of the leading causes of death. Treatments are often limited due to their toxic side effects, thus restraining the dosages and durations of such interventions. Combination therapies that target multiple pathways and/or molecules of the cancer cell and tumor microenvironment provide increased efficacy and safety. Developments in combinatorial virus and nanoparticle-based drug delivery and immunotherapy provide promising treatment options. One such advancement is the utilization of plant viruses and virus-like nanoparticles, which offer advantages in production and safety compared with mammalian-based vectors, for in situ vaccination to stimulate antitumor immune responses locally and distally. However, which plant viruses and virus-like nanoparticles are most effective, and how they compare with traditional cancer therapies, are not well understood.

In the recent study by Lee et al., potato virus X–based nanoparticles were investigated either as a monotherapy or in combination or conjugation therapy with the DNA damaging and replication inhibiting chemotherapy doxorubicin to combat a mouse model of melanoma. The authors first observed that the potato virus X nanoparticles, when delivered in situ eight days post–tumor inoculation, were effective at limiting the tumor volume and extending mouse survival. Due to the chemical and physical properties of these virus-based nanoparticles, the authors attached doxorubicin at a ratio of ~850 doxorubicin molecules per each nanoparticle, with the hypothesis that this conjugate would have enhanced anticancer properties. However, this conjugate provided no advantage in reduction in tumor volume or survival compared with just nanoparticles or doxorubicin alone. Despite this, the combination treatment of free doxorubicin with nanoparticles displayed improved tumor suppression and mouse survival, along with the strongest stimulation of an anticancer immune response within the tumor microenvironment. This study provides early, but promising, evidence that timing, formulation, and administration route are important factors when utilizing combinatorial plant-based virus immunotherapy to attenuate tumor burden locally and potentially systemically. Future studies are still needed to optimize these emerging therapeutic paradigms and prove their safety and efficacy in the clinic.

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