Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma

Chimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3–synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3+CD147+), but not single antigen (GPC3-CD147+) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients

The effect of a micronutrient powder home fortification program on anemia and cognitive outcomes among young children in rural China: a cluster randomized trial

Abstract Background Anemia early in life has been associated with delayed cognitive and motor development. The WHO recommends home fortification using multiple micronutrient powders (MNPs) containing iron as a strategy to address anemia in children under two. We evaluated the effects of a program freely distributing MNP sachets to caregivers of infants in rural China. Methods We conducted a cluster-randomized controlled trial in Shaanxi province, enrolling all children aged 6–11 months in target villages. Following a baseline survey, investigators randomly assigned each village/cluster to a control or treatment group. In the treatment group, caregivers were instructed to give MNPs daily. Follow-up was after 6, 12, and 18 months of intervention. Primary outcomes were hemoglobin concentrations and scores on the Bayley Scales of Infant Development. Results One thousand, eight hundred and-two eligible children and their caregivers were enrolled. At baseline 48% (870) of children were anemic and 29% (529) were developmentally delayed. Six hundred and-ten children (117 villages) were assigned to the control group and 1192 children (234 villages) were assigned to the treatment group. Assignment to the treatment group was associated with an improvement in hemoglobin levels (marginal effect 1.77 g/L, 95% CI 0.017–3.520, p-value = 0.048) and cognitive development (marginal effect 2.23 points, 95% CI 0.061–4.399, p-value = 0.044) after 6 months but not thereafter. There were no significant effects on motor development. Zero effects after the first 6 months were not due to low compliance, low statistical power, or changes in feeding behavior. Hemoglobin concentrations improved in both the treatment and control groups over the course of the study; however, 22% (325) of children remained anemic at endline, and 48% (721) were cognitively delayed. Conclusions Providing caregivers with MNP sachets modestly hastened improvement in hemoglobin levels that was occurring absent intervention; however, this improvement did not translate into improved developmental outcomes at endline. Trial registration ISRCTN44149146 ; prospectively registered on 15th April 2013

Prevalence, risk factors and short-term consequences of adverse birth outcomes in Zimbabwean pregnant women: a secondary analysis of a cluster-randomized trial.

BACKGROUND: Globally, 15 million children are born preterm each year and 10.7 million are born at term but with low birthweight (<2500 g). METHODS: The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) cluster-randomized trial enrolled 5280 pregnant women between 22 November 2012 and 27 March 2015 to test the impact of improved water supply, sanitation and hygiene, and improved infant feeding, on child growth and anaemia. We conducted a secondary analysis to estimate the prevalence and risk factors of miscarriage, stillbirth, preterm birth, size small for gestational age (SGA), low birthweight (LBW), perinatal mortality, and neonatal mortality, and to estimate the effects of adverse birth outcomes on infant survival and growth. RESULTS: The prevalence of adverse birth outcomes was: miscarriage: 5.0% [95% confidence interval (CI), 4.4, 5.7]; stillbirth: 2.3% (95% CI 1.9, 2.7); preterm birth: 18.2% (95% CI 16.9, 19.5); SGA: 16.1% (95% CI 15.0, 17.3); LBW: 9.8% (95% CI 9.0, 10.7); and neonatal mortality: 31.4/1000 live births (95% CI 26.7, 36.5). Modifiable risk factors included maternal HIV infection, anaemia, lack of antenatal care and non-institutional delivery. Preterm infants had higher neonatal mortality [risk ratio (RR): 6.1 (95% CI 4.0, 9.2)], post-neonatal infant mortality [hazard ratio (HR): 2.1 (95% CI 1.1, 4.1)] and stunting at 18 months of age [RR: 1.5 (95% CI 1.4, 1.7)] than term infants; 56% of stillbirths and 57% of neonatal deaths were among preterm births. CONCLUSIONS: Neonatal mortality and stillbirth are high in Zimbabwe and appear to be driven by high preterm birth. Interventions for primary prevention of preterm birth and strengthened management of preterm labour and ill and small neonates are required to reduce neonatal mortality in Zimbabwe and other African countries with similar profiles

Using Conditionality as a Solution to the Problem of Low Uptake of Essential Services Among Disadvantaged Communities: A Social Determinants View

Conditional cash transfer schemes, which use cash to incentivize uptake of basic health and educational services, are well established among social planners in low and middle-income countries and are now taking hold in high-income countries. We appraised these schemes within a social determinants framework and found some encouraging signs in their first decade of operation. Success, however, has been inconsistent, and it is unclear whether conditional cash transfer schemes can reliably secure meaningful improvements in participants' health and nutritional status or educational attainment. Conditional cash transfer schemes' objectives will not be met unless they are transformed in 3 ways: transferring power as well as resources, emphasizing entitlements alongside conditionality, and avoiding the trap of incoherent or residualized policy. (Am J Public Health. Published online ahead of print June 16, 2011: e1-e5. doi:10. 2105/AJPH.2011.300140)