Translation of nanoparticles (NPs) into human clinical trials for patients with refractory cancers has lagged due to unknown biologic reactivities of novel NP designs. To overcome these limitations, simple well-characterized mRNA lipid-NPs have been developed as cancer immunotherapeutic vaccines. While the preponderance of RNA lipid-NPs encoding for tumor-associated antigens or neoepitopes have been designed to target lymphoid organs, they remain encumbered by the profound intratumoral and systemic immunosuppression that may stymie an activated T cell response. Herein, we show that systemic localization of untargeted tumor RNA (derived from whole transcriptome) encapsulated in lipid-NPs, with excess positive charge, primes the peripheral and intratumoral milieu for response to immunotherapy. In immunologically resistant tumor models, these RNA-NPs activate the preponderance of systemic and intratumoral myeloid cells (characterized by coexpression of PD-L1 and CD86). Addition of immune checkpoint inhibitors (ICIs) (to animals primed with RNA-NPs) augments peripheral/intratumoral PD-1+CD8+ cells and mediates synergistic antitumor efficacy in settings where ICIs alone do not confer therapeutic benefit. These synergistic effects are mediated by type I interferon released from plasmacytoid dendritic cells (pDCs). In translational studies, personalized mRNA-NPs were safe and active in a client-owned canine with a spontaneous malignant glioma. In summary, we demonstrate widespread immune activation from tumor loaded RNA-NPs concomitant with inducible PD-L1 expression that can be therapeutically exploited. While immunotherapy remains effective for only a subset of cancer patients, combination therapy with systemic immunomodulating RNA-NPs may broaden its therapeutic potency.

Objectives/Hypothesis Head and neck cancer pain is a prevalent problem, and the current opioid crisis has highlighted concerns raised in chronic pain management. This study assessed the characteristics of opioid use in patients undergoing treatment for oropharynx cancer and identified risk factors associated with chronic opioid use. Study Design Retrospective cohort study. Methods A study was conducted of 198 eligible patients who underwent radiotherapy as part of their treatment for oropharynx cancer at a single institution from 2012 to 2017. p16/human papillomavirus (HPV) status was determined by pathology report review. Opioid use was recorded. Statistical analysis was performed to assess risk factors for chronic opioid use and effect on overall survival. Results The average age was 62 years, and the mean follow‐up was 38 months. Eighty‐three percent of patients had stage III/IV disease, and 73% received chemoradiotherapy. Sixty‐nine percent were HPV/p16 positive. Fifty‐seven (29%) patients had preexisting chronic pain conditions. Chronic opioid use was observed in 53% of the patients. Age ≤ 62 years (P < .0001), history of depression (P = .0356), p16 negative status (P = .0097), opioid use at pretreatment visit (P = .0021), and presence of a preexisting chronic pain condition at time of diagnosis (P = .0181) were associated with chronic opioid use using univariate analysis. On multivariate analysis, T stage and anxiety/depression were associated with chronic opioid use. Overall survival was worse for patients who had chronic opioid use, but was not significant when recurrence was taken into consideration. Conclusions More than 50% of the patients treated for oropharynx squamous cell carcinoma in this cohort were chronic opioid users after treatment. Identifying patients at greatest risk for chronic opioid use prior to treatment may help with long‐term pain management in this patient population. Level of Evidence 4 Laryngoscope, 129:2087–2093, 2019

CD70-specific CAR-T cells specifically recognized and efficiently eliminated CD70-positive HNSCC cells. This study provides the basis for further investigation into CD70 and other CAR-T targets.

No abstract

No abstract