Programable Albumin-Hitchhiking Nanobodies Enhance the Delivery of STING Agonists to Potentiate Cancer Immunotherapy.

Stimulator of interferon genes (STING) is a promising target for potentiating antitumor immunity, but multiple pharmacological barriers limit the clinical utility, efficacy, and/or safety of STING agonists. Here we describe a modular platform for systemic administration of STING agonists based on nanobodies engineered for hitchhiking of agonist cargo on serum albumin. Using site-selective bioconjugation chemistries to produce molecularly defined products, we found that covalent conjugation of a STING agonist to anti-albumin nanobodies improved pharmacokinetics and increased cargo accumulation in tumor tissue, stimulating innate immune programs that increased the infiltration of activated natural killer cells and T cells, which potently inhibited tumor growth in multiple mouse tumor models.

STING-Activating Polymer-Drug Conjugates for Cancer Immunotherapy.

The stimulator of interferon genes (STING) pathway links innate and adaptive antitumor immunity and therefore plays an important role in cancer immune surveillance. This has prompted widespread development of STING agonists for cancer immunotherapy, but pharmacological barriers continue to limit the clinical impact of STING agonists and motivate the development of drug delivery systems to improve their efficacy and/or safety. To address this challenge, we developed SAPCon, a STING-activating polymer-drug conjugate platform based on strain-promoted azide-alkyne cycloaddition of dimeric-amidobenzimidazole (diABZI) STING agonists to hydrophilic polymer chains through an enzyme-responsive chemical linker.

Cannabis Retail Market Indicators in Five Legal States in the United States: A Public Health Perspective.

Purpose: Adult-use cannabis markets are operating in multiple US states and abroad. Sales and licensing data for alcohol and tobacco are often used to understand consumption patterns and evaluate policy changes. Cannabis market data may provide similar insights, although these newly legal markets are complex and evolving, and the state data structures can differ.

A Research Agenda to Inform Cannabis Regulation: How Science Can Shape Policy.

In the United States, changes to cannabis policy have outpaced scientific knowledge about cannabis, its effects, and the impacts of different policy approaches. Research barriers stem from key federal policies, including strict drug scheduling of cannabis, which comprehensively hinder the ability to conduct cannabis research, affecting state markets, evidence-based regulation, and scientific gains that could more effectively shape policy moving forward. The Cannabis Regulators Association (CANNRA) is a nonpartisan nonprofit organization that convenes and supports government agencies to facilitate information exchange and learning from existing cannabis regulations across US states and territories and other governmental jurisdictions.