No abstract

Currently, there is a huge demand to develop chemoimmunotherapy with reduced systemic toxicity and potent efficacy to combat late-stage cancers with spreading metastases. Here, we report several “cocktail” therapeutic formulations by mixing immunogenic cell death (ICD)–inducing chemotherapeutics and immune adjuvants together with alginate (ALG) for localized chemoimmunotherapy. Immune checkpoint blockade (ICB) antibody may be either included into this cocktail for local injection or used via conventional intravenous injection. After injection of such cocktail into a solid tumor, in-situ gelation of ALG would lead to local retention and sustained release of therapeutics to reduce systemic toxicity. The chemotherapy-induced ICD with the help of immune adjuvant would trigger tumor-specific immune responses, which are further amplified by ICB to elicit potent systemic antitumor immune responses in destructing local tumors, eliminating metastases and inhibiting cancer recurrence. Our strategy of combining clinically used agents for tumor-localized cocktail chemoimmunotherapy possesses great potential for clinical translation.

Osteoporosis is the most prevalent metabolic bone disease that affects half the women in the sixth and seventh decade of life. Osteoporosis is characterized by uncoupled bone resorption that leads to low bone mass, compromised microarchitecture and structural deterioration that increases the likelihood of fracture with minimal trauma, known as fragility fractures. Several factors contribute to osteoporosis in men and women. In women, menopause – the cessation of ovarian function, is one of the leading causes of primary osteoporosis. Over the past three decades there has been growing appreciation that the adaptive immune system plays a fundamental role in the development of postmenopausal osteoporosis, both in humans and in mouse models. In this review, we highlight recent data on the interactions between T cells and the skeletal system in the context of postmenopausal osteoporosis. Finally, we review recent studies on the interventions to ameliorate osteoporosis.

Stroke is second leading cause of death in China, however, there are very few data available in the English literature to reflect the burden. We summarize the current epidemiological trends and estimate of the burden of stroke in recent reports available in Chinese.

Immunotherapy with toll like receptor 9 (TLR9) agonist CpG ODN offers an emergent strategy to treat life-threatening malignant glioma. CpG is typically applied invasively by intracranial and intrathecal administration which induces not only poor compliance and lessened potency but also possibly strong adverse effects and immunotoxicity. Here, it is reported that immunotherapy of murine LCPN glioma is greatly boosted by polymersome-steered intravenous and intranasal brain delivery of CpG. CpG is efficiently loaded in apolipoprotein E peptide-directed polymersomes to give blood-brain barrier permeable and glioma and cervical lymph node-homing CpG nano-immunoadjuvant (t-NanoCpG) which strongly stimulates the maturation of dendritic cells, antigen cross-presentation, and production of proinflammatory cytokines in vivo. Intriguingly, both intravenous and intranasal administration of t-NanoCpG brings about significant survival benefits in murine LCPN glioma-bearing mice while free CpG and nontargeted CpG nano-immunoadjuvant (NanoCpG) afford modest therapeutic effects. Moreover, combination of t-NanoCpG with radiotherapy further boosts the immunotherapeutic effects leading to more improved survival rate of mice. This intelligent brain-permeable nano-immunoadjuvant provides a new, minimally invasive and highly potent strategy for immunotherapy of glioma.